Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and radiographic screening for the current study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXPatients with known central nervous system (CNS) involvement may be excluded; however, if CNS disease is cleared before the treatment with nivolumab, patients could be allowed if no permanent CNS damageXx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, with the following exceptions: \r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of clinical stability upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to randomization\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXChildren who have histologically proven diagnoses of the following types of CNS tumor are eligible for entry onto this protocol; the exclusive focus is on medulloblastoma and other CNS primitive neuro-ectodermal tumors (PNET) of the brain or spinal cordXx_NEWLINE_xXAll children less than 120 months (10years) of age, irrespective of clinical stage, with a diagnosis of any of the following CNS PNET are eligible: pineoblastoma, all primary CNS-PNET, including CNS/cerebral neuroblastoma, CNS/cerebral ganglioneuroblastoma, medulloepithelioma, ependymoblastoma, embryonal tumor with abundant neuropil and true rosettes (ETANTR; more recently designated as \embryonal tumor with multilayered rosettes\ or \ETMR\), melanotic medulloblastoma and/or medullomyoblastoma, CNS supratentorial PNET, spinal cord PNET, brainstem PNET are all eligible, regardless of patterns of (divergent) differentiationXx_NEWLINE_xXAll diagnoses other than medulloblastoma and CNS PNET - these include: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord.; All choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)Xx_NEWLINE_xXPatients with CNS tumors or known CNS metastases will be excluded from this trial; patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows not evidence for active disease; patients with extra axial disease (e.g. skull [bone] metastasis that do not invade the dura) may enroll if there is no evidence for CNS edema associated with the lesionXx_NEWLINE_xXPatients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowedXx_NEWLINE_xXPart A: Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumorsXx_NEWLINE_xXPart C: Patients with relapsed or refractory medulloblastoma or CNS PNETXx_NEWLINE_xXPatients are eligible if central nervous system (CNS) metastases are adequately treated and neurological symptoms have returned to baseline or are controlled for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent); patients with untreated CNS metastases are eligible if they are not symptomatic and the lesions are less than 1 cm in sizeXx_NEWLINE_xXREGISTRATION STEP 2-RANDOMIZATION: Patients must not be known to have AML in the CNSXx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXPatient must be CNS (cerebrospinal fluid [CSF]) negative for leukemiaXx_NEWLINE_xXPatients with central nervous system (CNS) metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.\r\n** No neurosurgical resection or brain biopsy within 28 days prior to randomization\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to randomization \r\n** Screening CNS radiographic study >= 28 days from completion of radiotherapy and >= 14 days from discontinuation of corticosteroidsXx_NEWLINE_xXPatients must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration; patients with CNS3 are excluded from the trial; patients with CNS1 or CNS2 will be eligible, but will be monitored for CNS involvement; note that intrathecal methotrexate administered during the pre-study lumbar puncture may count as the first dose of intrathecal therapy required as part of the studyXx_NEWLINE_xXPatients with known or suspected central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded; however, subjects with controlled brain metastases will be allowed to enroll; controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for at least 2 weeks, and no new or progressive neurological signs and symptomsXx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to treatment start\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXPatients with central nervous system (CNS) metastases with the following exceptions: Patient untreated CNS metastases with 5 or fewer sites of disease, with no single site larger than 20 mm, are eligible if they are asymptomatic and not requiring steroids at any dose; patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays; patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)Xx_NEWLINE_xXParticipants with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria:\r\n* Disease outside the CNS is present\r\n* No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* Not requiring anti-convulsants for symptomatic control\r\n* Minimum of 3 weeks between completion of CNS radiotherapy and cycle 1 day 1 and recovery from significant (grade >= 3) acute toxicity with no ongoing requirement for corticosteroidXx_NEWLINE_xXPatients with known active CNS leukemia.Xx_NEWLINE_xXUntreated central nervous system (CNS) metastases or CNS metastases that have progressedXx_NEWLINE_xXSubject has current central nervous system (CNS) or leptomeningeal metastases or history of CNS or leptomeningeal metastases.Xx_NEWLINE_xXSubjects with CNS disease must have been on a stable dose of steroids for 2 weeks prior to their biopsy and must not have progressive hydrocephalus at enrollment.Xx_NEWLINE_xXPatients must not have active central nervous system (CNS) involvement (by clinical evaluation); patients with previous documented history of CNS involvement of acute leukemia, or with clinical signs or symptoms consistent with CNS involvement of acute leukemia, must have a lumbar puncture which is negative for CNS involvement of acute leukemia; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture before registration; note that treatment with intrathecal therapy is recommended during protocol treatment but CNS analysis during treatment is not requiredXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 3 months prior to first dose of study drug; screening with CNS imaging studies (CT or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXPatients with CNS GCTs who are newly diagnosed are excluded from the studyXx_NEWLINE_xXELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C): Patients must not have active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days; previously treated CNS disease with documented cleared CSF will be allowedXx_NEWLINE_xXELIGIBILITY CRITERIA - PHASE II (ARM D): Patients must not have active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days; previously treated CNS disease with documented cleared CSF will be allowedXx_NEWLINE_xXSubjects with known active or history of CNS involvement by malignancyXx_NEWLINE_xXUntreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment at enrollmentXx_NEWLINE_xXParticipants with primary CNS malignancies or tumors with CNS metastases as the only site of disease, will be excludedXx_NEWLINE_xXParticipants with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease (patients with controlled brain metastasis allowed to enroll)Xx_NEWLINE_xXPatients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: disease outside the CNS is present; no clinical evidence of progression since completion of CNS-directed therapy; minimum of 2 weeks between completion of radiotherapy and cycle 1 day 1 and recovery from significant (grade ? 3) acute toxicity with no ongoing requirement for > 10 mg of prednisone per day or an equivalent dose of other corticosteroid; NOTE: patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatmentXx_NEWLINE_xXUntreated or symptomatic central nervous system (CNS) metastases (CNS imaging not required). Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and do not require intervention such as surgery, radiation, or any corticosteroid therapy for management of symptoms related to CNS diseaseXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for ? 6 months prior to randomization; Note: Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXHas CNS metastases or symptomatic CNS involvementXx_NEWLINE_xXKnown CNS disease including, but not limited to, metastasesXx_NEWLINE_xXClinically asymptomatic and stable central nervous system (CNS) metastases are allowed (including untreated CNS metastases) if they have not required increasing doses of steroids or stable doses equivalent to prednisone > 10 mg daily within 2 weeks prior to study entry for CNS symptomsXx_NEWLINE_xXCentral nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* >= 28 days from prior therapy completion (including radiation and/or surgery) to registration\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXParticipants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatmentXx_NEWLINE_xXSubjects with symptomatic CNS metastases who are neurologically unstable and/or require an increased dose of steroid to manage CNS symptoms within 1 week prior to the first day of treatment are excluded\r\n* Subjects with brain or leptomeningeal metastases that do not meet the above criteria are allowed\r\n* Symptomatic disease is allowed as long as symptoms are controlled and stableXx_NEWLINE_xXHave known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with treated CNS metastases are eligible for this study if they have not received corticosteroids and/or anticonvulsants within 7 days of study treatment, and their disease is asymptomatic and radiographically stable for at least 60 days.Xx_NEWLINE_xXPatients with asymptomatic CNS involvement are allowed.Xx_NEWLINE_xXSymptomatic CNS involvement.Xx_NEWLINE_xXKnown CNS metastasesXx_NEWLINE_xXCNS metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last 3 months prior to randomization.Xx_NEWLINE_xXKnown CNS involvement at diagnosisXx_NEWLINE_xXActive, non-stable brain metastases or CNS diseaseXx_NEWLINE_xXPresence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks.Xx_NEWLINE_xXParticipants must have progressive CNS lesions, as defined by one of the following:\r\n* Patients may have multiple progressive CNS lesions, some of which have been treated by stereotactic radiosurgery (SRS) or surgery; patients are eligible if they have one or more untreated (by surgery or SRS) progressive lesions that is measurable\r\n* Patients have measurable residual or progressive lesions after surgery\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis); biopsy can be considered for definitive diagnosis\r\n* Patients who have previously been treated with systemic therapy for CNS metastases are eligibleXx_NEWLINE_xXAcute symptomatic CNS hemorrhageXx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** There are no more than 3 lesions, =< 1 cm in size each\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXCOHORT 1: Has known active central nervous system (CNS) leukemia; subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapyXx_NEWLINE_xXCOHORT 2: Has known active central nervous system (CNS) leukemia; subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapyXx_NEWLINE_xXPatients having active central nervous system (CNS) metastases; patients adequately treated and neurologically returned to baseline (except for residual signs of symptoms related to the CNS treated) for at least 2 weeks prior to enrolment are allowed; in addition, patients must be either off corticosteroids or on a stable or decreasing dose of < 10 mg daily prednisone or equivalentXx_NEWLINE_xXAny uncontrolled neurological symptom attributed to CNS metastasisXx_NEWLINE_xXSubjects may not have presence of active CNS disease or extramedullary disease.Xx_NEWLINE_xXSymptomatic central nervous system (CNS) metastasis(es). Note: Baseline CT/MRI of the brain is required for SCLC patients enrolled in Arm 4. Patients with previously treated CNS metastasis(es) are eligible if the patients with previously treated CNS metastasis(es) are asymptomatic and radiographically/clinically stable and not requiring steroids within 4 weeks prior to first dose. Note: Non-SCLC patients without clinical signs or symptoms of CNS involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) scan of the brain unless it is considered standard of care.Xx_NEWLINE_xXKnown CNS disease including, but not limited to, metastasesXx_NEWLINE_xXParticipants with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases\r\n* Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvementXx_NEWLINE_xXClinical Evidence of CNS diseaseXx_NEWLINE_xXSymptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.Xx_NEWLINE_xXPatients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 4 weeks and must be off steroid treatment for 2 weeks prior to study enrollmentXx_NEWLINE_xXNew or progressive CNS lesions, as assessed by the patient’s treating physician\r\n* It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one lesion is measurable (>= 10 mm) per RECIST 1.1; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Patients who have had prior cranial surgery are eligible provided that there is evidence of measurable residual or progressive lesions, and at least 3 months have passed since surgery; if a patient has surgical resection followed by whole brain radiation therapy (WBRT), then there must be evidence of progressive CNS disease after the completion of WBRT\r\n* Patients who had had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions that have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression\r\n* Patient who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such patients must be asymptomatic or minimally symptomatic from their CNS metastases and not requiring corticosteroidsXx_NEWLINE_xXGrade 1 or higher CNS hemorrhage on baseline brain MRI, or history of grade 2 or higher CNS hemorrhage within 12 monthsXx_NEWLINE_xXCNS metastases if not previously treated and stable for at least 2 months per imaging and clinical assessment.Xx_NEWLINE_xXHave central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ?14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted.Xx_NEWLINE_xXCNS lymphoma.Xx_NEWLINE_xXPatients with primary CNS tumors or symptomatic CNS metastases who have not undergone surgery and/or radiotherapy and/or who are not neurologically stable;Xx_NEWLINE_xXPreviously untreated CNS metastases or progressive CNS metastasesXx_NEWLINE_xXSubjects with central nervous system metastasis; with the exception of subjects who have stable brain metastases as defined as off steroids and no CNS progress for 6 months after CNS treatment.Xx_NEWLINE_xXParticipants with known or suspected uncontrolled CNS metastases or with the CNS as the only site of active diseaseXx_NEWLINE_xXHave metastasis to the CNS that is symptomatic and/or requires therapy with corticosteroids or anti-convulsant medication. However, subjects who have completed treatment (radiation therapy) for CNS metastases and do not require continued treatment with corticosteroids or anti-convulsants may be enrolled in this study.Xx_NEWLINE_xXParticipants with known untreated brain metastases should be excluded from this clinical trial; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to study entry; subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first study treatmentXx_NEWLINE_xXSubjects with active (i.e. symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, the subject is off corticosteroids for at least 2 weeks and the subject is neurologically stable.Xx_NEWLINE_xXSymptomatic and/or untreated CNS metastasesXx_NEWLINE_xXNo uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >= 2 weeks since definitive CNS therapy (radiation or surgery) and >= 2 weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entryXx_NEWLINE_xXPatients with secondary metastasis to the CNS are eligible if they have met certain criteria.Xx_NEWLINE_xXSubject has confirmed central nervous system (CNS) involvement by DLBCL. Subjects at risk for CNS involvement per Investigator assessment must receive prophylaxis. For subjects at risk, or with any neurological symptoms, testing for CNS involvement is required at Screening.Xx_NEWLINE_xXHistory of unstable central nervous system (CNS) metastases or seizure disorder related to the malignancy; however, those subjects who were treated for prior CNS metastases and who are asymptomatic may participate in the study as long as they are not receiving treatment with steroids.Xx_NEWLINE_xXCNS status \r\n* Subjects with ALL\r\n** Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\r\n*** CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of white blood cells (WBCs)\r\n*** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin positive for blasts\r\n**** CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts\r\n**** CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm\r\n* Subjects with lymphoma\r\n** Subjects must have no signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at the time of screening; subjects who have previously been treated for CNS disease and who have the following CNS status will be eligible:\r\n*** CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs\r\n*** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS 2a: < 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithmXx_NEWLINE_xXSubjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence of >= 5/uL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia)Xx_NEWLINE_xXCNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicityXx_NEWLINE_xXActive CNS involvementXx_NEWLINE_xXNo uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >= 2 weeks since definitive CNS therapy (radiation or surgery) and >= 2 weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entryXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXParticipants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excludedXx_NEWLINE_xXEXCLUSION - TREATMENT: Central nervous system (CNS) abnormalities: presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of cerebrospinal fluid (CSF) with ? 5 white blood cells (WBCs) per mm^3; history or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvementXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXPatients with treated central nervous system (CNS) metastases will be eligible if not symptomatic, the CNS disease has been stable for a minimum of 6 weeks and the patient requires less than or equal to the equivalent of 2 mg/day of dexamethasoneXx_NEWLINE_xXPatients with known symptomatic CNS metastases or lepotomeningeal disease requiring steroids.Xx_NEWLINE_xXPatients with known involvement of the CNS by malignancy will be excluded.Xx_NEWLINE_xXPart A: Patients with recurrent or refractory non-CNS solid tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except patients with extra-cranial germ-cell tumors who have elevations of serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); patients in part A cannot have CNS metastasesXx_NEWLINE_xXMalignant CNS disease that has not been definitively treatedXx_NEWLINE_xXSubject has symptomatic CNS metastases.Xx_NEWLINE_xXPresence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy (e.g. radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. Patients with treated brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study enrollment) and off of steroids for at least 2 weeks before administration of any study treatment.Xx_NEWLINE_xXEvidence of CNS involvement by NHLXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and subjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)Xx_NEWLINE_xXKnown active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS involvement with their lymphoma must have completed effective treatment of their CNS disease at least 3 months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant CNS imagingXx_NEWLINE_xXHas known active central nervous system (CNS) leukemia; subjects with previously treated CNS disease may participate provided they are stable (without evidence of active disease by imaging for at least 4 weeks prior to the first dose of treatment, and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to D1 of treatmentXx_NEWLINE_xXPatients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptomsXx_NEWLINE_xXIf patient has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: Patient has measurable disease outside CNS; Patient does not have metastases to midbrain, pons, medulla or spinal cord; Patient is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); Patient has not had whole-brain radiation within 6 weeks prior to study enrollment; Patient has stable CNS disease as demonstrated by at least 4 weeks of stability between the last intervention scan and the study screening scanXx_NEWLINE_xXSubjects with a history of or active CNS tumors or metastases from non-CNS tumors.Xx_NEWLINE_xXActive CNS involvement of their malignancy.Xx_NEWLINE_xXThe patient has known active or suspected brain or leptomeningeal metastases. (Central nervous system [CNS] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 3 months following radiation therapy or other locoregional ablative therapy to the CNS.Xx_NEWLINE_xXRadiographic evidence of CNS metastasesXx_NEWLINE_xXSubjects with CNS lesions are excludedXx_NEWLINE_xXPatients with uncontrolled central nervous system (CNS) metastatic involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is:\r\n* > 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening\r\n* Not receiving steroid therapy\r\n* Not receiving anti-convulsive medications that were started for brain metastasesXx_NEWLINE_xXActive CNS involvement by malignant cells (? 2 months from the conditioning)Xx_NEWLINE_xXCNS metastatic involvementXx_NEWLINE_xXActive or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments; participants with a history of treated asymptomatic CNS metastases are eligibleXx_NEWLINE_xXSubjects with radiologically-detected active CNS lymphoma, leptomeningeal CNS disease or isolated CNS disease which are eligible for definitive CNS directed radiation therapy will be excludedXx_NEWLINE_xXPatients diagnosed with primary CNS tumorsXx_NEWLINE_xXPresence of active central nervous system (CNS) leukemia. Subjects adequately treated for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for leukemia cells are eligible. Subjects with no history of CNS leukemia will not be required to undergo cerebrospinal fluid sampling for eligibility.Xx_NEWLINE_xXKnown central nervous system (CNS) involvement by lymphoma; patients at high risk for secondary CNS involvement but without neurologic symptoms suspected to be due to lymphoma are allowed to be enrolled and receive intrathecal chemotherapy including but not limited to methotrexate, cytarabine and glucocorticoids; patients who are enrolled and subsequently identified to have pathologic confirmation of CNS involvement by lymphoma may be continued on study at the discretion of the principal investigatorXx_NEWLINE_xXSymptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring > 5 mg/day of dexamethasone (or equivalent) to control CNS disease; note: patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed > 2 weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entryXx_NEWLINE_xXSymptomatic or untreated Central nervous system (CNS) disease, Subjects with a history of CNS disease (leukemia, lymphoma or myeloma) are permitted to enrol if they have previously received appropriate therapy and CNS remission has been documented. Subject with primary CNS lymphoma (defined as isolated CNS lymphoma without systemic involvement) are excluded from study.Xx_NEWLINE_xXSymptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS diseaseXx_NEWLINE_xXPatients with active central nervous system (CNS) metastases or leptomeningeal involvement by tumor (patients with a history of brain metastases who have successfully treated for brain metastasis by surgery or radiation and who have not had any evidence of the new or progressive CNS disease for more than 12 months are eligible)Xx_NEWLINE_xXIf they have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trialXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease, are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.Xx_NEWLINE_xXTREATMENT WITH SJCAR19: CNS-1/CNS-2 disease with neurologic changesXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases with significant neurological compromise or symptoms are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy), who show no evolving new neurological symptoms are eligible for the study.Xx_NEWLINE_xXActive central nervous system (CNS) disease\r\n* Definition: any patient receiving active CNS therapy (defined as more than 1 intrathecal treatment per week or current radiation therapy to brain); if patient has a history of CNS disease: must have cerebrospinal fluid (CSF) sampling within 28 days of enrollment that is negative for leukemia; intrathecal chemotherapy for patients without active CNS disease is allowed (e.g., ongoing primary or secondary prophylaxis for patients who cleared the CSF prior to study enrollment); CSF sample is not required for enrollment for patients with no history of CNS diseaseXx_NEWLINE_xXKnown clinically active central nervous system (CNS) involvement; prior evidence of CNS involvement successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment and there are no neurological signs of potential CNS involvementXx_NEWLINE_xXKnown, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.Xx_NEWLINE_xXKnown clinically active CNS involvement.Xx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligibleXx_NEWLINE_xXCentral nervous system (CNS) status\r\n* Subjects with leukemia with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\r\n** CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of white blood cells (WBCs)\r\n** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n*** CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin positive for blasts\r\n*** CNS 2b: ? 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts\r\n*** CNS 2c: ? 10/uL RBCs; ? 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm\r\n* Subjects with lymphoma\r\n** Subjects must have no signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at the time of screening; subjects who have been previously treated for CNS disease but have no evidence of disease at screening are eligibleXx_NEWLINE_xXSubjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence of ? 5/uL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia and/or radiographic signs of leptomeningeal disease)Xx_NEWLINE_xXPrimary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)Xx_NEWLINE_xXActive (i.e., symptomatic or progressing) CNS metastases. Subjects with CNS metastases are eligible for the trial if:Xx_NEWLINE_xXKnown or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 daysXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.Xx_NEWLINE_xXPatients must not have known non-controlled CNS metastasis.Xx_NEWLINE_xXHistory or clinical signs of meningeal or active CNS involvementXx_NEWLINE_xXSubjects with symptomatic untreated CNS metastases are excluded\r\n* Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment\r\n* In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatmentXx_NEWLINE_xXNo progression of CNS metastases on MRI or CT for at least 14 days after last day of prior therapy for the CNS metastasesXx_NEWLINE_xXPatients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemiaXx_NEWLINE_xXParticipants with primary central nervous system (CNS) tumors, or with CNS metastases as the only site of active disease (Participants with controlled brain metastases; however, will be allowed to enroll)Xx_NEWLINE_xXConcurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted. Patients with a known history of CNS disease or leukemic brain metastasis must have been treated locally, have at least 3 consecutive lumbar punctures (LPs) with no evidence of CNS leukemia, and must be clinically stable for at least 4 weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable).Xx_NEWLINE_xXPatients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.Xx_NEWLINE_xXClinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is required only if there is a clinical suspicion of CNS involvement by leukemia during screening.Xx_NEWLINE_xXCNS abnormalitiesXx_NEWLINE_xXPresence of CNS-3 disease or CNS-2 disease with neurological changesXx_NEWLINE_xXPatients with treated or untreated asymptomatic CNS metastases may be allowed to enroll.Xx_NEWLINE_xXPatients with primary CNS tumors are ineligible.Xx_NEWLINE_xXConcurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowedXx_NEWLINE_xXPatients with central nervous system (CNS) progression (parenchymal but not leptomeningeal) are eligible if CNS metastases are treated and deemed stable (with a repeat computed tomography [CT]/magnetic resonance imaging [MRI] imaging study) prior to the enrollment date; if radiation is used to treat CNS parenchymal disease, a 2 week washout period will applyXx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy or symptomatic CNS metastases.\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS.\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm).\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage.\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.\r\n** No neurosurgical resection or brain biopsy within 28 days prior to start of study treatment.\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to start of study treatment.\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids.Xx_NEWLINE_xXParticipants must not have suspected, known, or progressive CNS metastases, have untreated CNS metastases, or have the CNS as the only site of diseaseXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and\r\nsubjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a dose of less than 10 mg per dayXx_NEWLINE_xXDose Escalation Cohorts: Active CNS disease, including history of CNS metastases.Xx_NEWLINE_xXMTD/MFD Expansion Cohorts: CNS disease, including history of CNS metastases, that was not stable during the last 6 months.Xx_NEWLINE_xXAny history of CNS metastases that is not adequately treated (surgery or radiation) > 14 days prior to registrationXx_NEWLINE_xXKnown, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.Xx_NEWLINE_xXHistory of primary CNS malignancy, or leptomeningeal disease or CNS metastasesXx_NEWLINE_xXKnown untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria:\r\n* Presence of measurable disease outside the CNS\r\n* No radiographic evidence of worsening upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed)\r\n* Absence of leptomeningeal diseaseXx_NEWLINE_xXPatients requiring radiation for CNS diseases are excluded (CNS defined as brain soft tissue/intra parenchymal metastases within the gray and white matter of the brain and/or for cerebrospinal fluid [CSF] disseminated disease, including leptomeningeal carcinomatous disease)Xx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeks.Xx_NEWLINE_xXParticipants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded (controlled brain metastases will be allowed to enroll)Xx_NEWLINE_xXCNS involvement with disease refractory to intrathecal chemotherapyXx_NEWLINE_xXCNS status \r\n* Subjects with ALL\r\n** Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\r\n*** CNS 1, defined as absence of blasts in CSF on cytospin preparation, regardless of the number of white blood cells (WBCs);\r\n*** CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:\r\n**** CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;\r\n**** CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm\r\n* Subjects with DLBCL\r\n** Subjects must have no signs or symptoms of CNS disease or no detectable evidence of CNS disease on magnetic resonance imaging (MRI) at the time of screening; subjects who have been previously treated for CNS disease but have no evidence of disease at screening are eligibleXx_NEWLINE_xXCNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicityXx_NEWLINE_xXSubjects with primary central nervous system (CNS) tumor or CNS tumor involvement. However, subjects with metastatic CNS tumors may participate in this study if the subject is: > 4 weeks from prior therapy completion (including radiation and/or surgery); clinically stable with respect to the CNS tumor at the time of study entry; not receiving steroid therapy in treating CNS tumor or CNS tumor involvement; not receiving anti-convulsive medications (that were started for brain metastases).Xx_NEWLINE_xXKnown or suspected central nervous system (CNS) metastases, unless at least one month has passed since last local CNS therapy and there is no evidence for recurrent or progressive CNS disease on follow up imaging; participants may remain on steroids for CNS disease if they are taking a stable doseXx_NEWLINE_xXPatients with untreated, controlled asymptomatic central nervous system (CNS) lesions are allowed in this trial as long as the CNS is not a site of progressive disease on alectinib monotherapy; if the CNS is a site of progressive disease on alectinib monotherapy, treatment of CNS lesions is required for enrollmentXx_NEWLINE_xXParticipants who experienced progression of CNS lesions on alectinib who have not received local CNS therapies (radiation, surgery) to address the lesions; CNS imaging obtained at least 21 days after completion of radiation is required for confirmation of responseXx_NEWLINE_xXhave known uncontrolled or symptomatic CNS metastases;Xx_NEWLINE_xXSymptomatic brain or central nervous system (CNS) metastases; previously treated and stable CNS disease is allowedXx_NEWLINE_xXHas known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement; subjects with prior CNS involvement by lymphoma must have remission of the CNS component of the lymphoma; these subjects must have a baseline magnetic resonance imaging (MRI) during screening without evidence of new or enlarging brain lesions and must not have any new or progressive neurologic symptomsXx_NEWLINE_xXPatients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least 6 weeks prior to study registration in the opinion of the investigator and does not require corticosteroids (of any dose) for symptomatic management\r\n* NOTE: Only patients with a known history or indication of CNS disease are required to have CNS imaging prior to study entryXx_NEWLINE_xXActive or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments; subjects with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:\r\n* Evaluable or measurable disease outside the CNS\r\n* No metastases to midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n* No history of intracranial or spinal cord hemorrhage\r\n* No evidence of significant vasogenic edema\r\n* o ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose allowed\r\n* No stereotactic radiation, whole-brain radiation within 4 weeks prior to cycle 1 day 1\r\n* Subjects with CNS metastases treated by neurosurgical resection or brain biopsy within 3 months prior to cycle 1 day 1 will be excluded\r\n* Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study\r\n* Screening CNS radiographic study >= 4 weeks since completion of radiotherapy or surgical resection and >= 2 weeks since discontinuation of corticosteroidsXx_NEWLINE_xXSubject has symptomatic CNS metastases.Xx_NEWLINE_xXPatients with a history of central nervous system (CNS) involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for cyclophosphamide (Cy)/TBI arm; patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollmentXx_NEWLINE_xXKnown active DLBCL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis).Xx_NEWLINE_xXSubjects with CNS metastases are only eligible if the CNS metastases are treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment); in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)Xx_NEWLINE_xXActive CNS metastases; however, patients with CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be off steroids.Xx_NEWLINE_xXCentral nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: \r\n* Are asymptomatic, and \r\n* Have no requirement for steroids or enzyme-inducing anti-convulsants in the prior 28 daysXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligibleXx_NEWLINE_xXPatients with known history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to study registration and do not require corticosteroids (of any dose) for symptomatic management\r\n* NOTE: CNS imaging is only required at baseline for patients with known history of CNS metastasesXx_NEWLINE_xXPatients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI obtained within 4 weeks of registration or progressive neurological decline\r\n* Patients with primary CNS lymphoma who develop systemic recurrence following standard therapy may be included as long as no active CNS disease is present at the time or enrollment; similarly, patients with secondary involvement of the CNS from a systemic lymphoma may be included as long as the CNS disease has been optimally treated and they demonstrate no evidence of active CNS diseaseXx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy =< 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation =< 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\nNo neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXSubject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.Xx_NEWLINE_xXActive CNS disorder or seizure disorder or known CNS disease or neurologic symptomatology; in case of AML active CNS involvement as detected by lumbar puncture or neuro-imaging (only to be done if clinically indicated)Xx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** Screening CNS radiographic study ? 4 weeks from completion of radiotherapy and ? 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXCentral nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXPatients with known central nervous system (CNS) involvement may be excluded; however, if CNS disease is cleared before the treatment with nivolumab, patients could be allowed if no permanent CNS damageXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXIn the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and avelumab will be at least 14 days OR at least 5 half-lives for cytotoxic/noncytotoxic agents, whichever is longer; the toxicity from prior therapy should have resolved to grade =< 1, however alopecia and sensory neuropathy grade =< 2 is acceptable; the half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochures, or drug-administration manuals) and will be documented in the protocol eligibility document; use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and will not require a washout; concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted; patients with CNS disease or leukemic brain metastasis must have been treated locally and be clinically stable for at least 2 weeks prior to enrollment and have no ongoing neurological symptoms that are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable)Xx_NEWLINE_xXPatients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemiaXx_NEWLINE_xXPatients are excluded if they have active CNS metastases. Patients with history of CNS metastases must have MRI scans that show stability of brain metastases for 8 weeks.Xx_NEWLINE_xXCNS involvement with malignancy.Xx_NEWLINE_xXPatients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least 6 weeks prior to study registration in the opinion of the investigator and do not require corticosteroids (of any dose) for symptomatic management; NOTE: Patients are not required to have CNS imaging prior to study entryXx_NEWLINE_xXSubjects with history of central nervous system (CNS) disease are allowed if at the time of day 1 of the study there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least 2 weeks prior to the first study drug administration in a subject with no clinical signs of CNS diseaseXx_NEWLINE_xXUncontrolled central nervous system (CNS) metastases (i.e. known CNS lesions that are radiographically unstable, symptomatic and/or requiring escalating doses of corticosteroids)Xx_NEWLINE_xXSubjects with untreated symptomatic central nervous system (CNS) metastases are excluded\r\n* Subjects are eligible if symptomatic CNS metastases are treated and subjects have neurologically returned to baseline (except for residual signs and symptoms related to CNS treatment) for at least 7 days prior to first dose of study treatment\r\n** Subjects must be off corticosteroids for at least 7 days prior to first dose of study treatmentXx_NEWLINE_xXPatients with untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease) are excluded\r\n* Note: Subjects with previously treated CNS metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management are permitted to enrollXx_NEWLINE_xXSerious concurrent medical condition including CNS disorders.Xx_NEWLINE_xXKnown or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 daysXx_NEWLINE_xXKnown or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 daysXx_NEWLINE_xXmCRPC EXPANSION COHORT: Patients with evidence of CNS metastasis or leptomeningeal disease within 1 year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicatedXx_NEWLINE_xXKnown active CNS metastases and/or carcinomatous meningitis a. To be eligible for the study treatment, subjects must have stable disease ? 1 month, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications.Xx_NEWLINE_xXHas known active central nervous system (CNS) involvement; subjects with previously treated CNS disease may participate provided they are stable (without evidence of CNS leukemia at the time of screening and any neurologic symptoms have returned to baseline) and are not using steroids for at least 7 days prior to trial treatmentXx_NEWLINE_xXSubjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imagingXx_NEWLINE_xXSubjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imagingXx_NEWLINE_xXFor lymphodepletion chemotherapy, JCAR014 and durvalumab: Subjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imagingXx_NEWLINE_xXPrevious CNS surgery within 2 weeks of treatment, with the exception of biopsyXx_NEWLINE_xXPatients with untreated or symptomatic metastatic central nervous system (CNS) disease; however patients with CNS involvement may participate if:\r\n* Clinically stable with respect to the CNS tumor at the time of screening and > 2 weeks from prior therapy completion (including radiation and/or surgery) to the start of study treatment\r\n* Not on steroid therapy\r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases (these include carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, and vigabatrin)Xx_NEWLINE_xXActive central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior or currently treated brain metastases are allowed.Xx_NEWLINE_xXActive central nervous system (CNS) lymphoma within two weeks of registration; patients with a history of CNS involvement must have adequate treatment as defined by at least two negative spinal fluid assessments separated by at least one week; (otherwise lumbar puncture [LP] is not required if no clinical suspicion or evidence of CNS involvement); patients who have received cranial radiation therapy must still be eligible to receive total lymphoid irradiation to 7 GyXx_NEWLINE_xXAt screening, patients with =< 3 CNS metastases and each =< 1 cm size that were treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 30 days after definitive treatment, and if the patients with CNS metastases are not taking prednisone > 10 mg or equivalent dailyXx_NEWLINE_xXAt screening, patients with > 1 cm or > 3 in number treated CNS metastases may be included if there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, and if the patients with CNS metastases are not taking prednisone > 10 mg or equivalent dailyXx_NEWLINE_xXPatients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone > 10 mg or equivalent steroid daily will be excludedXx_NEWLINE_xXPatients with =< 3 untreated CNS metastases but with at least one lesion > 1 cm or peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone > 10 mg or equivalent steroid daily will be excludedXx_NEWLINE_xXPatients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, or patients with CNS metastases of any status who are taking prednisone > 10 mg or equivalent will be excludedXx_NEWLINE_xXFor patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day 1 of the study and meet the following criteria:\r\n* At least 28 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or computed tomography (CT) after last day of treatment with radiation to the CNS metastases\r\n* At least 14 days since last dose of corticosteroids\r\n* Must not have leptomeningeal disease or cord compressionXx_NEWLINE_xXSubjects with signs or symptoms indicative of CNS involvement; a CNS evaluation should be performed as clinically appropriate to rule our CNS involvementXx_NEWLINE_xXPatient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases (including brain metastases) are eligible for the study provided they are clinically stable and have met ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXCNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicityXx_NEWLINE_xXSymptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1 to 2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then repeat imaging will be performed, if more than 4 weeks have elapsed from the last scanXx_NEWLINE_xXKnown active (untreated) central nervous system (CNS) metastases that require steroids; subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 2 weeks before study entry, defined as:\r\n* No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases\r\n* Asymptomatic and receiving either no or stable doses of anticonvulsants and total doses of corticosteroids equivalent to 10 mg of prednisone or lessXx_NEWLINE_xXPreviously untreated CNS metastasis or progressive CNS metastasisXx_NEWLINE_xXTumor lesions in the CNS are permitted but lesions must have been stable for at least 3 months prior to Cycle 1 Day 1 (C1D1). Stable CNS lesions are defined as not requiring steroid prophylaxis or other medications to prevent seizures or other complications associated with CNS lesions and no evidence of worsening of CNS disease.Xx_NEWLINE_xXIn the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of selinexor and sorafenib administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for cytotoxic/noncytotoxic agents; the use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal (IT) therapy for patients with controlled central nervous system (CNS) leukemia at the discretion of the PI and with the agreement of the sponsor; controlled CNS leukemia is defined by the absence of active clinical signs of CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous cerebrospinal fluid (CSF) evaluations; (2) use of one dose of cytarabine (up to 2 g/m^2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy; these medications will be recorded in the case-report formXx_NEWLINE_xXPHASE II: At least one measurable extra-CNS lesion based upon RECIST version 1.1; Note: participants with at least one CNS lesion >= 10 mm but no other measurable extra-CNS lesions will still be allowed to participateXx_NEWLINE_xXHistory of hemorrhagic CNS metastasesXx_NEWLINE_xXRelapsed/refractory leukemia in 2nd or greater relapse or who have failed at least one re-induction attempt after relapse or for refractory disease. Patients must meet the WHO classification with ? 5% blasts in the bone marrow or must have definitive extramedullary disease (e.g. chloromas, skin lesions). Patients may have asymptomatic CNS 1 or CNS 2 disease, but not CNS 3 or symptomatic CNS disease. ORXx_NEWLINE_xXRelapsed/refractory non-CNS solid tumor that has not responded or has relapsed and for which no standard treatment is available. Patients may not have primary CNS tumors or CNS metastases. Lymphoma patients are permitted. Patients do not need to have measurable disease.Xx_NEWLINE_xXKnown active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomizationXx_NEWLINE_xXPatients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases are to be stable for > 3 months after treatment and off steroid treatment prior to study enrollmentXx_NEWLINE_xXKnown CNS metastases, unless stable and asymptomatic. Subjects with CNS metastases may be eligible for the study, provided:Xx_NEWLINE_xXThere is no evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.Xx_NEWLINE_xXPatients with active or prior central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells; NOTE: these patients are usually treated with CNS directed therapy; screening for cerebrospinal fluid (CSF)/CNS involvement is NOT required but can be performed per treating medical doctor (MD) discretionXx_NEWLINE_xXSymptomatic CNS metastases or CNS metastases requiring steroidsXx_NEWLINE_xXPatients with recurrent or progressive AT/RT or MRT (either CNS and/or extra-CNS) with radiographically measurable disease as defined by at least one lesion that can be measured in two dimensions or with tumor cells present in the CSF taken within 2 weeks prior to enrollmentXx_NEWLINE_xXSubject has uncontrolled metastases to the central nervous system (CNS) based on head CT or MRI. Subjects with brain metastases may be eligible 2 weeks after definitive therapy to all known sites of CNS disease provided they are asymptomatic and either off or on a non-increasing dose (in last 2 weeks) of systemic steroids and not on anticonvulsants for seizure activity directly related to progressive CNS metastases.Xx_NEWLINE_xXPatients with central nervous system (CNS) 1 or CNS 2 disease are eligible; patients with isolated CNS relapse or CNS 3 disease are not eligibleXx_NEWLINE_xXIndividuals with CNS 3 leukemiaXx_NEWLINE_xXUncontrolled CNS metastasesXx_NEWLINE_xXPatients with non central nervous system (CNS) primary tumors who have known brain metastases or symptomatic CNS disease (e.g., cranial nerve abnormalities) without cytologic abnormality in the cerebrospinal fluid (CSF) should be excluded from this clinical trial; patients with metastatic CNS tumors will not be excluded from enrollment on this study in the phase I component onlyXx_NEWLINE_xXHistory of CNS involvement by MMXx_NEWLINE_xXSuspected, known, or progressive CNS metastases (Imaging required only if participants are symptomatic)Xx_NEWLINE_xXPatients must not have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolledXx_NEWLINE_xXPHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients with evidence of central nervous system (CNS) metastasis, spinal cord compression, or leptomeningeal disease within one year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicatedXx_NEWLINE_xXPHASE II STUDY COHORT 1 OVARIAN CANCER ELIGIBILITY CRITERIA (MEDI+O, MEDI+C AND MEDI+O+C):\r\nPatients with evidence of CNS metastasis, spinal cord compression, or leptomeningeal disease within one year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with spinal cord compression may be considered if the condition is medically managed and currently asymptomaticXx_NEWLINE_xXPHASE II STUDY COHORT 5 TRIPLE NEGATIVE BREAST CANCER ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nPatients with evidence of CNS metastasis, spinal cord compression, or leptomeningeal disease within six months prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression free for the six months period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with spinal cord compression may be considered if the condition is medically managed and currently asymptomaticXx_NEWLINE_xXPHASE II STUDY METASTATIC CASTRATE-RESISTANT PROSTATE CANCER COHORT 4 ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nPatients with evidence of CNS metastasis, spinal cord compression, or leptomeningeal disease within 1 year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with spinal cord compression may be considered if the condition is medically managed and currently asymptomaticXx_NEWLINE_xXKnown active CNS metastases and/or carcinomatous meningitis • To be eligible for the study treatment, subjects must have stable disease ? 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medicationsXx_NEWLINE_xXUntreated CNS disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 2 weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease or symptoms.Xx_NEWLINE_xXActive central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior, or currently treated brain metastases are allowed.Xx_NEWLINE_xXKnown active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at the time of registration; prophylactic intrathecal chemotherapy is not a criterion for exclusionXx_NEWLINE_xXPatients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemiaXx_NEWLINE_xXCurrent CNS involvement by diseaseXx_NEWLINE_xXALK-positive NSCLC patients with asymptomatic central nervous system (CNS) metastases who are neurologically stable or have not required increasing doses of steroids within the 2 week prior to study entry to manage CNS symptomsXx_NEWLINE_xXNon-ALK-positive NSCLC patients with CNS metastasis should have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroidsXx_NEWLINE_xXEvidence of clinically significant central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosingXx_NEWLINE_xXPatients with symptomatic brain metastases are excluded; however, patients with asymptomatic central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior local treatment for CNS metastases > 28 days prior to study entry including radiotherapy or surgery; patients receiving steroids for CNS metastases may not participate on this studyXx_NEWLINE_xXConcurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated; such treatment may continue until the planned course is completed; subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvementXx_NEWLINE_xXPatients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are metXx_NEWLINE_xXPatients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions)Xx_NEWLINE_xXResearch participants with CNS involvement by leukemia, if deemed to be controlled and treatable by study team, at the time of enrollment are eligible; however, the CNS disease has to have been adequately treated with complete resolution of CNS leukemia confirmed by cerebral spinal fluid (CSF) analysis and imaging studies (if applicable) to be eligible to proceed with lymphodepletionXx_NEWLINE_xXPatients with active CNS diseaseXx_NEWLINE_xXActive CNS disease as identified by positive CSF cytospin at time of enrollmentXx_NEWLINE_xXActive CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ?1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.Xx_NEWLINE_xXPatients with primary CNS tumors as well as patients with CNS metastases are excluded.Xx_NEWLINE_xXRANDOMIZED PHASE II (ARMS K AND L): Patient must have no current or prior history of CNS involvementXx_NEWLINE_xXIf prior CNS leukemia, it must be treated and in CNS complete remission (CR)Xx_NEWLINE_xXSymptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; NOTE: patients with treated CNS metastases without evidence of progression and without uncontrolled symptoms or need for steroids may enrollXx_NEWLINE_xXPatients with active known CNS lymphoma. Patients with history of CNS leukemia now in remission are eligible for the trial.Xx_NEWLINE_xXPatient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 4 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis on brain imaging within 4 weeks of enrollment (2) off steroids for 2 weeks. Patients with clinically insignificant brain metastases that do not require treatment are eligibleXx_NEWLINE_xXPatients with stable and clinically insignificant central nervous system (CNS) disease are allowed; patients must be off steroids with no new CNS symptoms or findings on radiographic imaging for 1 monthXx_NEWLINE_xXPatients with known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:\r\n* No evidence of new or enlarging CNS metastasis\r\n* Off steroids that are used to minimize surrounding brain edema; patients with clinically insignificant brain metastases that do not require treatment are eligibleXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXHave either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.Xx_NEWLINE_xXHave or do not have active (untreated or progressing) CNS metastases.Xx_NEWLINE_xXActive central nervous system (CNS) metastases; magnetic resonance imaging (MRI) (or computed tomography [CT]) required within 3 months of starting treatment for all tumor types known to commonly metastasize to the brain (i.e. all tumors except pancreas, colorectal, ovarian) and for all patients with CNS symptoms that may represent CNS metastases; metastases which have been treated with radiotherapy > 2 months prior to start of protocol therapy and are asymptomatic (off steroid therapy for at least 1 month) may be included; patients must have had normal or stable (if treated, no new lesions) brain imaging (CT or MRI) within the two months prior to day 1 of study drug\r\n* For the NSCLC expanded cohort only: radiation =< 14 days prior to day 1 of study drug; subjects must be off steroids for > 14 days prior to day 1 of study drug and anticonvulsants must be discontinuedXx_NEWLINE_xXSubjects who have metastasis to the brain are eligible for IV administration; however, any CNS lesion must be inactive; prior metastasis that has been treated and is no longer present is acceptable; no metastases to the CNS (brain or spine) of non-CNS solid tumors may be injected due to the potential for swelling at the injection siteXx_NEWLINE_xXAt the time of enrollment, specified baseline CNS conditions must be =< grade II toxicity per Common Terminology Criteria for Adverse Events (CTCAE) 3.0 criteria; this includes the following conditions: arachnoiditis/meningismus/radiculitis, ataxia, CNS cerebrovascular ischemia, CNS necrosis/cystid progression, cognitive disturbance, confusion, dizziness, encephalopathy, hydrocephalus, leak - cerebrospinal fluid, leukoencephalopathy (radiologic findings), mental status, psychosis, seizure, somnolence/depressed level of consciousnessXx_NEWLINE_xXPatients with CNS metastasis at presentation will not be eligibleXx_NEWLINE_xXAll patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for studyXx_NEWLINE_xXPatients must be free of active or ongoing ischemic or degenerative CNS disease and no active or resistant CNS leukemiaXx_NEWLINE_xXPatients with a history of central nervous system (CNS) tumor involvement are eligible if they have completed treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered from or stabilization of the side effects associated with the therapy and have no evidence of progressive CNS disease at the time of enrollmentXx_NEWLINE_xXKnown, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.Xx_NEWLINE_xXSymptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.Xx_NEWLINE_xXUncontrolled CNS metastases, primary CNS tumors, or solid tumors with CNS metastases as only measurable disease;Xx_NEWLINE_xXPatients with active central nervous system (CNS) lymphoma or active cerebrospinal fluid (CSF) involvement with malignant cells requiring CNS-specific therapy with IV or intrathecal (IT) methotrexate (MTX); Note: Patients with any prior CNS lymphoma (parenchymalor leptomeningeal) MUST be in complete remission (CR) in those compartments without any maintenance therapy requiredXx_NEWLINE_xXKnown central nervous system (CNS) primary tumor, CNS metastases or carcinomatous meningitis (Part A). Patients may be enrolled with CNS metastasis in certain circumstances in Part B.Xx_NEWLINE_xXActive CNS metastases.Xx_NEWLINE_xXPresence of symptomatic or uncontrolled central nervous system (CNS) metastases requiring local CNS-directed treatment.Xx_NEWLINE_xXPatients with CNS metastases with the following exceptions:Xx_NEWLINE_xXPatient untreated CNS metastases with 4 or fewer sites of disease, with no single site larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays.Xx_NEWLINE_xXPatients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent).Xx_NEWLINE_xXEvidence for active CNS involvement by leukaemiaXx_NEWLINE_xXPatients with symptomatic CNS metastases;Xx_NEWLINE_xXExtramedullary leukemia allowed except CNS diseaseXx_NEWLINE_xXCNS leukemiaXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXPatients with known CNS metastases (Patients with any clinical signs of CNS metastases must have a CT or MRI of the brain to rule out CNS metastases in order to be eligible for participation in the study). Patients who have had brain metastases treated with radiotherapy or surgically removed with no residual disease confirmed by imaging; patients should be clinically stable and off corticosteroid treatment at least 3 weeks prior to randomization).Xx_NEWLINE_xXPatients with active CNS diseaseXx_NEWLINE_xXExtramedullary (CNS) disease;Xx_NEWLINE_xXPatients with symptomatic CNS metastases.Xx_NEWLINE_xXKnown symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they (1) have completed their treatment and have recovered from the acute effects of radiation therapy and/or surgery prior to enrollment, (2) have discontinued corticosteroid treatment for these metastases for at least 14 days, and (3) are neurologically stable;Xx_NEWLINE_xX210 Evidence of CNS involvement by NHL.Xx_NEWLINE_xXUntreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed.Xx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days before initiation of study treatment\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days before initiation of study treatment\r\n** Screening CNS radiographic study ? 4 weeks from completion of radiotherapy and ? 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXHistory or presence of clinically relevant CNS pathologyXx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to randomization\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 4 weeks prior to randomization.\r\n** Screening CNS radiographic study 4 weeks from completion of radiotherapy and 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXIf they have untreated central nervous system (CNS) metastasis; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trialXx_NEWLINE_xXKnown, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is requiredXx_NEWLINE_xXUntreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed as per protocol-defined criteria.Xx_NEWLINE_xXActive or symptomatic central nervous system (CNS) disease\r\n* For study purposes, a subject will not be considered as having active CNS disease if the subject has documentation of prior CNS disease and has received prior treatment (IT or radiation) and is:\r\n** Asymptomatic for the last 28 days prior to screening and\r\n** Has documented at least 2 negative cerebrospinal fluid (CSF) cytology (which must include 1 lumbar puncture [LP] within the study screening window)Xx_NEWLINE_xXPatients with treated stable CNS metastases that are asymptomatic (including leptomeningeal carcinomatosis) are allowed, if there is no evidence of progression for at least 4 weeks after CNS-directed treatment as ascertained by clinical examination and brain imaging. Patients requiring steroids must be at a stable or decreasing dose (?10 mg/day dexamethasone or equivalent) for at least 2 weeks prior to the start of treatment. The use of seizure prophylaxis is allowed.Xx_NEWLINE_xXSymptomatic and/or untreated central nervous system (CNS) metastases; patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeksXx_NEWLINE_xXAsymptomatic or symptomatic CNS metastasis allowedXx_NEWLINE_xXPreviously-treated or untreated CNS metastasis allowedXx_NEWLINE_xXStable dose of corticosteroids for CNS metastasis for > 7 daysXx_NEWLINE_xXPatients with seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for > 14 daysXx_NEWLINE_xXSymptomatic and/or untreated or actively progressing central nervous system (CNS) metastases or leptomeningeal disease. Patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:Xx_NEWLINE_xXPatients with Gilbert's disease or known CNS metastatic disease. However, patients with CNS metastases who are asymptomatic and have completed a course of therapy are eligible for the study provided that they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new enlarging CNS metastasis, (2) off steroids or on a stable dose of steroids.Xx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy =< 28 days prior to registration\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation =< 28 days prior to registration\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXUntreated brain metastases or neurologically unstable central nervous system (CNS) metastases (CNS metastases will be considered stable if there are no new nor enlarging lesions for one month, and the patient remains off steroids and anti-epileptics for the same time period)Xx_NEWLINE_xXKnown cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required)Xx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy or symptomatic CNS metastases\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n* Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXStratum 1: Recurrent or refractory primary malignant central nervous system (CNS) tumor patients \r\n* Patients with a histologically confirmed diagnosis of a primary malignant non-brainstem CNS tumor (excluding DIPG patients) that is recurrent, progressive, or refractory; all tumors must have histologic verification at either the time of diagnosis or recurrence except patients with marker (+) CNS germ cell tumorsXx_NEWLINE_xXAny active CNS metastasesXx_NEWLINE_xXCentral nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms.Xx_NEWLINE_xXPatients must have no history of central nervous system (CNS) metastasis at the screening assessment\r\n* NOTE: Patients with stable brain metastases (mets) which have been treated are eligible; patients with suspected symptoms of CNS metastasis should undergo CNS imaging at the time of screening to rule out active metastasisXx_NEWLINE_xXPatients with CNS disease or other sites of extra-pulmonary metastases at the time of most recent episode of disease recurrence preceding enrollmentXx_NEWLINE_xXPatients with active or untreated central nervous system (CNS) disease; patients previously treated for CNS disease must be asymptomatic and must not be using steroids for at least 4 weeks prior to starting the study treatmentXx_NEWLINE_xXPatients with a history of ventral nervous system (CNS) myeloma or other CNS malignancy.Xx_NEWLINE_xXPatients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 3 months and must be off steroid treatment prior to study enrollmentXx_NEWLINE_xXAny active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; NOTE: patients treated with stereotactic radiotherapy or surgery are eligible if no evidence of CNS disease progression >= 4 weeks and patients must be off corticosteroid therapy for >= 3 weeks; NOTE: carcinomatous meningitis is excluded regardless of clinical stabilityXx_NEWLINE_xXParticipants who have a primary central nervous system (CNS) malignancy, or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); individuals with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:\r\n* Evaluable or measurable disease outside the CNS\r\n* Radiographic demonstration of stability upon the completion of CNS directed therapy and no evidence of interim progression (for at least 4 weeks prior to the first dose of study drug) between the completion of CNS-directed therapy and the screening radiographic procedure\r\n* The screening CNS radiographic procedure is >= 8 weeks since completion of radiotherapy and >= 4 weeks since the discontinuation of corticosteroids and anticonvulsants\r\n* Note: These exceptions do not include carcinomatous meningitis which is excluded regardless of clinical stabilityXx_NEWLINE_xXPatients with symptomatic central nervous system (CNS) metastases or leptomeningeal carcinomatosis should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; exceptions include patients with previously-treated CNS metastases or those with are asymptomatic, subcentimeter metastases, and have no requirement for steroids or anti-seizure medication for at least one week prior to study entry; screening with CNS imaging studies (CT scan or MRI) is requiredXx_NEWLINE_xXPatients with untreated malignant involvement of the central nervous system (CNS) should be excluded from this clinical trial; head imaging will be necessary to document absence of CNS involvement in patients with colon/rectal cancer and soft tissue sarcomas; patients with hematologic malignancies who have undergone treatment for malignant involvement of the CNS must have no evidence of residual disease by imaging or cerebrospinal fluid (CSF) sampling prior to study enrollmentXx_NEWLINE_xXPatients with a history of prior central nervous system (CNS) metastases or skull lesions with intracranial extension will be required to have a head computed tomography (CT) or magnetic resonance imaging (MRI) at study entry demonstrating no active CNS metastases; patients with skull metastases with associated intracranial soft tissue masses will remain eligibleXx_NEWLINE_xXCohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other\n             central nervous system (CNS) metastases are only permitted if treated, asymptomatic,\n             and stable (not requiring steroid for at least 4 weeks prior to the start of study\n             treatment). Cohort B only: Patients with CNS metastases or leptomeningeal\n             carcinomatosis are excluded.Xx_NEWLINE_xXKnown active central nervous system (CNS) metastases or carcinomatous meningitis; patients with CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; however, oral corticosteroids for control of CNS symptoms are not allowed on studyXx_NEWLINE_xXUntreated central nervous system (CNS) metastasis; if treated CNS metastasis/es, treatment of CNS disease (surgery or radiation) must have been completed at least 30 days prior to registration; patients could still be on steroidsXx_NEWLINE_xXPatient with uncontrolled or symptomatic central nervous system (CNS) metastases; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy and are clinically stable and have discontinued prior treatment with anticonvulsantsXx_NEWLINE_xXPatients with CNS involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion ((including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXPatients with asymptomatic untreated CNS disease may be enrolled after consultation, provided all of the following criteria are met:\r\n* Evaluable or measurable disease outside the CNS\r\n* No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n* No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1Xx_NEWLINE_xXPatients with asymptomatic treated CNS metastases may be enrolled after consultation, provided all the criteria listed above are met as well as the following:\r\n* Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1\r\n* Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXPatients who have a CNS toxicity > grade 2 are not eligibleXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXSubject has symptomatic/untreated CNS diseaseXx_NEWLINE_xXPatients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression)Xx_NEWLINE_xXPatients with refractory or recurrent solid tumors or lymphomas, excluding CNS tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse; patients with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligibleXx_NEWLINE_xXPatients with primary CNS tumors are not eligibleXx_NEWLINE_xXPatients with prior history of or known metastatic CNS disease involvement are not eligible; (Note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated)Xx_NEWLINE_xXPatients who have a known primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollmentXx_NEWLINE_xXPatients with central nervous system (CNS) involvement may participate if the patient is:\r\n* >= 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening\r\n* Not receiving steroid therapyXx_NEWLINE_xXStage 1 solid tumor and stage 2 endometrial and ovarian cancer participants with known central nervous system (CNS) metastatic lesions which are symptomatic and/or growing; patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll; brain metastasis must be stable for 1 month with verification by imaging (brain MRI completed at screening demonstrating no current evidence of progressive brain metastases); CNS imaging will not be mandated for asymptomatic patients with no history of CNS metastasesXx_NEWLINE_xXFor Part C (Phase 2): recurrent ALL patients with CNS 3 status are not eligibleXx_NEWLINE_xXKnown active central nervous system (CNS) leukemia or lymphoma – patients with previously treated CNS disease are permitted if neurologically stable with no ongoing or anticipated need for steroid therapy are eligibleXx_NEWLINE_xXAt screening, patients with CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatmentXx_NEWLINE_xXPatients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excludedXx_NEWLINE_xXPatients with =< 3 untreated CNS metastases but with at least one lesion > 1 cm or peri-tumoral edema will be excludedXx_NEWLINE_xXPatients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapyXx_NEWLINE_xXAt screening, patients with =< 3 treated CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatmentXx_NEWLINE_xXPatients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excludedXx_NEWLINE_xXPatients with =< 3 untreated CNS metastases but with at least one lesion > 1 cm or peri-tumoral edema will be excludedXx_NEWLINE_xXPatients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapyXx_NEWLINE_xXPatients with central nervous system (CNS) metastases or a history of CNS metastases are ineligibleXx_NEWLINE_xXPHASE II: Patients with CNS metastases or a history of CNS metastases are ineligibleXx_NEWLINE_xXPatients who have a primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollmentXx_NEWLINE_xXSubjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: \r\n* CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of white blood cells (WBCs); \r\n* CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm\r\n* CNS3 with marrow disease who has failed salvage systemic and intensive intrathecally (IT) chemotherapy (and therefore not eligible for radiation)\r\n* Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least 1800 cGy)Xx_NEWLINE_xXPatients with active CNS metastasesXx_NEWLINE_xXPatients with active central nervous system (CNS) metastases are excluded; patients with CNS metastases that have been treated must be off steroid treatment for > 2 months and be asymptomatic; patients that have symptoms to suggest CNS metastases should have a brain magnetic resonance imaging (MRI) within 28 days of enrollment to confirm the absence of CNS metastases; contrast computed tomography (CT) is acceptable for patients who are unable to undergo a brain MRIXx_NEWLINE_xXUntreated central nervous system (CNS) metastases or symptomatic CNS metastases requiring escalating doses of corticosteroidsXx_NEWLINE_xXPatients with CNS progression during the trial will be allowed to receive local treatment for CNS metastases and will remain on protocol; trial medications will be held during the time patients are receiving radiation therapy as dictated by their treating physiciansXx_NEWLINE_xXPatients with central nervous system (CNS) tumors or known CNS metastases are not eligible; patients with a history of CNS metastases that have been surgically resected are eligible only if the baseline evaluation shows no evidence of current CNS metastases; patients with any evidence of CNS metastases on baseline evaluation are not eligible, regardless of whether the lesions have been previously treated and/or appear stableXx_NEWLINE_xXPatients with a history of central nervous system (CNS) involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible; patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollmentXx_NEWLINE_xXSubjects with symptomatic CNS metastases.Xx_NEWLINE_xXSubjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.Xx_NEWLINE_xXUntreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressedXx_NEWLINE_xXSubjects with untreated CNS metastases are excluded.Xx_NEWLINE_xXUntreated central nervous system (CNS) metastases or CNS metastases that have progressedXx_NEWLINE_xXCNS metastasesXx_NEWLINE_xXKnown CNS metastases or leptomeningeal disease: For Part 1, patients with CNS metastases treated with whole brain radiotherapy, gamma knife, and/or surgery who are considered stable by CNS imaging and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled. For Part 2, patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or surgery who are considered stable by CNS imaging for at least 2 months prior to enrollment and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled.Xx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXPatients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their CTL019 infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings. Patients with other forms of active CNS-3 leukemic involvement such as CNS parenchymal or ocular disease, cranial nerve involvement or significant leptomeningeal disease are not eligible. However, such patients with other forms of CNS-3 leukemic involvement (non-CSF involvement) are eligible if there is documented evidence of disease stabilization for at least 3 months prior to CTL019 infusion. Patients must have no acute/ongoing neurologic toxicity > Grade 1 with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past 3 months.Xx_NEWLINE_xXPatients with untreated or symptomatic metastatic central nervous system (CNS) disease; however patients with CNS involvement may participate if:\r\n* Clinically stable with respect to the CNS tumor at the time of screening and > 4 weeks from prior therapy completion (including radiation and/or surgery) to the start of study treatment\r\n* Not receiving steroid therapy \r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases (these include carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, and vigabatrin)Xx_NEWLINE_xXKnown symptomatic central nervous system (CNS) metastases. Participants with a history of treated or untreated asymptomatic CNS metastases may be eligible.Xx_NEWLINE_xXKnown active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening.Xx_NEWLINE_xXKnown CNS lymphoma or leukemia.Xx_NEWLINE_xXKnown CNS lymphoma or leukemia.Xx_NEWLINE_xXPatient with CNS involvement unless he/she is at least 4 weeks from prior therapy completion to starting the study treatment and has stable CNS tumor at time of screening and not receiving steroids and/or enzyme inducing ant-epileptic medications for brain metastasesXx_NEWLINE_xXActive CNS leukemiaXx_NEWLINE_xXThe patient has known active or suspected CNS leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.Xx_NEWLINE_xXRadiological evidence of CNS metastasesXx_NEWLINE_xXSymptomatic, untreated CNS metastasesXx_NEWLINE_xXHas active central nervous system (CNS) metastases (including evidence of cerebral edema by MRI, or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28 days of study treatment.Xx_NEWLINE_xXSubject has primary central nervous system (CNS) tumor or known CNS metastases and/or history of CNS metastases and/or carcinomatous meningitis; Exception: Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be off corticosteroids for 4 weeks prior to enrollment.Xx_NEWLINE_xXSubjects with radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]) a. Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well-controlled and stable for at least 28 days after receiving local therapy (irradiation, surgery, etc.)Xx_NEWLINE_xXActive CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.Xx_NEWLINE_xXCNS disease prophylaxis: CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)Xx_NEWLINE_xXActive signs or symptoms of CNS involvement by malignancyXx_NEWLINE_xXPatients who have central nervous system (CNS) involvement unless they meet ALL of the following criteria:\r\n* >= 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapyXx_NEWLINE_xXNo known central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells; these patients are usually treated with CNS directed therapy; screening for cerebrospinal fluid (CSF)/CNS involvement is NOT required but can be performed per treating medical doctor (MD) discretion; intrathecal (IT) methotrexate or IT cytarabine prophylaxis in patients with negative CSF who are felt to be at high risk of CNS relapse is allowed per local MD discretion; this should be noted on the treatment formXx_NEWLINE_xXPatients with primary CNS tumor or CNS tumor involvementXx_NEWLINE_xXEvidence of CNS involvement with DLBCLXx_NEWLINE_xXCNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.Xx_NEWLINE_xXHave symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.Xx_NEWLINE_xXKnown brain metastases, unless previously treated and patients are neurologically returned to baseline except for residual signs and symptoms related to Central Nervous System (CNS) treatment and CNS lesions are not progressive in size and number for 4 weeks.Xx_NEWLINE_xXEvidence of significant CNS haemorrhage i.e. CTCAE grade 2 or above;Xx_NEWLINE_xXKnown active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.Xx_NEWLINE_xXPatients with CNS malignancies (primary or metastatic)Xx_NEWLINE_xXCNS lymphoma involvementXx_NEWLINE_xXPatients with CNS metastases that are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off of steroids. The patient should be off steroids at least 14 days before pre-registration. Asymptomatic CNS metastatic disease without associated edema, shift, requirement for steroids or anti-seizure medications are eligible after discussion with the sponsor medical monitor. For patients with a history of CNS metastasis, baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)Xx_NEWLINE_xXPatients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)Xx_NEWLINE_xXPatients with a prior diagnosis of CLL/SLL in central nervous system (CNS) are eligible only if the CNS disease has been treated; patients must be neurologically stable, without progressive symptoms while off of steroids and anti-convulsants; at least 28 days must have elapsed since CNS treatment, and the patient must have recovered from all associated toxicities of treatment; patients who have transfusion-dependent thrombocytopenia or bleeding/coagulation disorders that may increase the risk of life-threatening bleeding are excludedXx_NEWLINE_xXA primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of the CNS. CNS imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the CNS.Xx_NEWLINE_xXSymptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease\r\n* Note: patients with controlled CNS metastases are allowed; radiotherapy or surgery for CNS metastases must have been completed > 2 weeks prior to study entry; patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging; steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entryXx_NEWLINE_xXPatients must not have active involvement of the central nervous system (CNS) with MM (by clinical evaluation); patients with documentation of, or clinical signs or symptoms consistent with, CNS involvement of MM must have a lumbar puncture that is negative for CNS involvement of MM; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture prior to registration; note that monitoring of CNS involvement and treatment with intrathecal therapy is recommended during protocol treatmentXx_NEWLINE_xXPatients with known brain metastasis are eligible only if by central nervous system (CNS) imaging there is no evidence of CNS progression at least 30 days following definitive CNS treatment (resection or radiation)Xx_NEWLINE_xXRecurrent/refractory CNS non-Hodgkin's lymphoma involving CNS (Brain, Cerebrospinal fluid (CSF) or intraocular compartments)Xx_NEWLINE_xXSymptomatic CNS metastasisXx_NEWLINE_xXCNS disease other than neurologically stable, treated brain metastases.Xx_NEWLINE_xXHistory of, or known central nervous system (CNS) involvement caused by the underlying B-cell malignancy or prior history of National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) Grade greater than or equal to >= 3 drug-related CNS toxicity. Participants with signs or symptoms of CNS involvement should have a computed tomography (CT) or magnetic resonance imaging (MRI)Xx_NEWLINE_xXCurrent or history of CNS lymphomaXx_NEWLINE_xXCNS metastasis that is symptomatic or progressing or untretaed or that required current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases)Xx_NEWLINE_xXPatient with CNS involvement unless they are at least 4 weeks from prior therapy completion to starting the study treatment and have stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastasesXx_NEWLINE_xXPatients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemiaXx_NEWLINE_xXKnown uncontrolled or symptomatic CNS metastasesXx_NEWLINE_xXPatient with CNS metastases.Xx_NEWLINE_xXSymptomatic or untreated central nervous system (CNS) leukemia. Subjects are permitted to enroll if previously treated for CNS disease, free of symptoms at the time of screening, and have not required intrathecal chemotherapy at least 1 month prior to study Day 1.Xx_NEWLINE_xXHave the presence of unstable central nervous system (CNS) metastasis. History of CNS metastasis or stable CNS metastases is allowed (no longer requiring active therapy such as steroid medications). Participants with a history of CNS metastases must have a brain scan (for example, magnetic resonance imaging [MRI]) within 28 days of randomization to document stability, even if there have been no changes in symptoms.Xx_NEWLINE_xXHistory or evidence of CNS disease. Radiographic screening of all participants without history of CNS metastasis is required.Xx_NEWLINE_xXCNS metastasis except adequately treated brain metastasis documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids for management of CNS symptomsXx_NEWLINE_xXPatients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastasesXx_NEWLINE_xXActive CNS lymphoma.Xx_NEWLINE_xXKnown uncontrolled or symptomatic CNS metastasesXx_NEWLINE_xXParticipants with a history of central nervous system (CNS) metastases prior to the initiation of first-line platinum-based chemotherapy must have received definitive local treatment and have documentation of stable or improved CNS disease statusXx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy, active or untreated CNS metastases, symptomatic CNS metastases, and/or leptomeningeal diseaseXx_NEWLINE_xXKnown active or suspected brain or leptomeningeal metastases. CNS imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement. Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 8 weeks following radiation therapy or other locoregional ablative therapy to the CNS.Xx_NEWLINE_xXHave untreated central nervous system (CNS) metastases. Patients are eligible for study participation if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 60 days prior to consent. In addition, patients must either be off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 60 days prior to consent.Xx_NEWLINE_xXPresence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy within prior 2 weeks.Xx_NEWLINE_xXActive and/or untreated CNS disease or non-stable brain metastasesXx_NEWLINE_xXPresence of CNS-3 disease and CNS-2 disease with neurological changesXx_NEWLINE_xXPresence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to Study DayXx_NEWLINE_xXAsymptomatic and adequately treated CNS metastases are not exclusionaryXx_NEWLINE_xXPatients with central nervous system (CNS) involvement may participate if they meet all the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screeningXx_NEWLINE_xXPatients with central nervous system (CNS) involvement unless they meet all of the following criteria: a. At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment. b. Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.Xx_NEWLINE_xXPatients with history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to study registrations and do not require corticosteroids (of any dose) for symptomatic managementXx_NEWLINE_xXHave symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required.Xx_NEWLINE_xXUncontrolled central nervous system (CNS) metastases; patients are considered to have controlled CNS metastases (and thus eligible) if they have completed local therapy (radiotherapy [XRT] and/or surgery) and are off steroids with clinical and radiographic stability 1 month from the end of CNS-directed therapyXx_NEWLINE_xXDiagnosis of CNS metastases for whom SRS or WBRT is indicated, as determined by radiation oncologist assessmentXx_NEWLINE_xXParticipant with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis Participants with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) ? 28 days (? 14 days for stereotactic radiosurgery) and, if on corticosteroid therapy, should be receiving a stable dose of no greater than 4 mg/d dexamethasone (or equivalent anti-inflammatory potency of another corticosteroid) for at least 14 days before start of study treatment). Patients must not be receiving corticosteroids for brain metastases.Xx_NEWLINE_xXSubjects with active central nervous system (CNS) metastases are excluded; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeksXx_NEWLINE_xXUntreated central nervous system (CNS) metastasis that are > 1 cm or symptomatic are not allowed; (patients with CNS metastases > 1 cm or symptomatic that have been treated and demonstrated to be radiologically and clinically stable for at least 4 weeks are allowed)Xx_NEWLINE_xXPrimary CNS lymphoma or evidence of CNS involvement by lymphomaXx_NEWLINE_xXLeptomeningeal carcinomatosis or other untreated or symptomatic central nervous system (CNS) metastases; patients with asymptomatic CNS metastases, other than leptomeningeal disease, are eligible provided they have been clinically stable without requiring increase in steroid dose for at least 4 weeksXx_NEWLINE_xXPatients must have previously received at least one CNS directed treatment (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgeryXx_NEWLINE_xXPatients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS diseaseXx_NEWLINE_xXHave symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.Xx_NEWLINE_xXCNS metastases that are symptomatic and /or requiring escalating doses of steroids.Xx_NEWLINE_xXPatients with central nervous system (CNS) involvement may participate if the patient meets all of the following criteria:\r\n* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment\r\n* Clinically stable with respect to the CNS tumor at the time of screening\r\n* Not receiving steroid therapy\r\n* Not receiving enzyme inducing anti-epileptic medications that were started for brain metastasesXx_NEWLINE_xXNo signs or symptoms of CNS metastases (mets) within the last 30 days (from enrollment evaluation)Xx_NEWLINE_xXCNS disease:Xx_NEWLINE_xXDose escalation and MTD/RP2D expansion cohort: Patients with symptomatic CNS metastases are excluded. Patients with treated CNS metastases or untreated asymptomatic CNS metastases not requiring immediate local therapy may be eligible. Enrollment of patients with metastases must be approved by the study medical monitor.Xx_NEWLINE_xXOptional CNS disease expansion cohort: Patients with asymptomatic untreated CNS metastases not needing immediate local therapy or patients with progressive CNS disease following local therapy may be eligible with medical monitor approval.Xx_NEWLINE_xXHistory of or current relevant CNS pathologyXx_NEWLINE_xXSuspected or known CNS metastasisXx_NEWLINE_xXSubjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.Xx_NEWLINE_xXEvidence of untreated CNS metastasesXx_NEWLINE_xXPART B: Patients with CNS metastases are eligible for enrollment if they have no overt evidence of neurological deficits, and are not requiring anti-epileptics or steroids to control their neurological symptoms; patients with known CNS metastases must have relevant CNS imaging performed approximately coincident with body imaging during response assessmentsXx_NEWLINE_xXPatients may have received any number of prior CNS directed therapies - there are no limitationsXx_NEWLINE_xXPatients who have received previous treatment with bevacizumab for CNS disease are not eligible for participationXx_NEWLINE_xXHave central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy); brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patientsXx_NEWLINE_xXPatients with a history of central nervous system (CNS) leukemia are eligible if they are not symptomatic from current CNS involvement\r\n* If there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordinglyXx_NEWLINE_xXNo clinical evidence of central nervous system (CNS) metastases (including carcinomatous meningitis) at baseline, with the exception of those patients who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) had no requirement for steroids or enzyme-inducing anticonvulsants within 6 months prior to registrationXx_NEWLINE_xXPatient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.Xx_NEWLINE_xXActive central nervous system (CNS) disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 2 weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease.Xx_NEWLINE_xXAny untreated CNS metastasesXx_NEWLINE_xXPatient with symptomatic or growing CNS metastatic lesionsXx_NEWLINE_xXKnown CNS disease, except for treated brain metastasisXx_NEWLINE_xXBrain metastases (unless stable disease >3 mos. by scan without additional CNS-directed therapy)Xx_NEWLINE_xXAbsence of CNS involvement by leukemia.Xx_NEWLINE_xXClinical evidence of active CNS leukemiaXx_NEWLINE_xXSubjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ?10mg daily prednisone (or equivalent)Xx_NEWLINE_xXActive central nervous system (CNS) disease\r\n* Subjects with a history of CNS metastases or cord compression are allowable if they have been clinically stable for at least 6 weeks since completion of definitive treatment, are off steroids (if the steroids were part of the CNS disease treatment), and in the case of brain metastases, have stable or improved imaging at least 6 weeks after completion of their definitive treatmentXx_NEWLINE_xXIn phase II study (PMLBL) patients with CNS involvement are not eligibleXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to registration; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXActive CNS metastasesXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastasesXx_NEWLINE_xXPresence of symptomatic CNS lymphomaXx_NEWLINE_xXIn cohort 2, eligible patients will include those who have CNS disease that is amenable for surgery (typically < 3 brain metastases and with planned resection by neurosurgery); these patients may include those who have received or not received previous treatment(s) for their CNSXx_NEWLINE_xXCohorts 1 and 3: Participants must have stable disease or be responders (partial response [PR] or complete response [CR]) to neratinib in the CNS at the time of non-CNS progressionXx_NEWLINE_xXCohort 2: Participants must have progressive disease in CNS or non-CNS sitesXx_NEWLINE_xXUntreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks.Xx_NEWLINE_xXKnown central nervous system (CNS) metastases or leptomeningeal carcinomatosis; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if the subject has clinical findings suggestive of CNS metastasisXx_NEWLINE_xXActive brain metastases with the exception of subject has been treated and are asymptomatic and there has been no evidence of CNS progression for at least 4 weeks of first dose of MEDI-573Xx_NEWLINE_xXPathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy; direct biopsy of central nervous system (CNS) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent; patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancyXx_NEWLINE_xXPatients planning to undergo radiosurgery to any CNS lesion OR patients planning to have surgical resection of ALL of their CNS lesionsXx_NEWLINE_xXPatients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to treatmentXx_NEWLINE_xXSymptomatic brain or central nervous system (CNS) metastases; previously treated and stable CNS disease is allowedXx_NEWLINE_xXKnown active CNS involvementXx_NEWLINE_xXPatient has known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; oral corticosteroids for control of CNS symptoms are allowedXx_NEWLINE_xXSymptomatic CNS diseaseXx_NEWLINE_xXBrain metastases permitted in Arms A and B if:\r\n* Central nervous system (CNS)-directed treatment has been given\r\n* No CNS-directed therapy for the past 3 months, including glucocorticoids AND\r\n* CNS disease has been clinically and radiographically stable for at least 8 weeksXx_NEWLINE_xXDistant metastases, including CNS and vertebral or meningeal involvementXx_NEWLINE_xXPatients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:\r\n* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:\r\n** Evaluable or measurable disease outside the CNS\r\n** No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)\r\n** No history of intracranial hemorrhage or spinal cord hemorrhage\r\n** No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted\r\n** No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1\r\n* Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:\r\n** Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study\r\n** No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1\r\n** Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroidsXx_NEWLINE_xXClinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease ? 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)Xx_NEWLINE_xXCentral nervous system (CNS) inclusion criteria:\r\n* Subjects without CNS metastases are eligible; Note: brain imaging is not required for asymptomatic subjects without known brain metastatic disease prior to enrollment into the study\r\n* Subjects with untreated asymptomatic CNS metastases not needing immediate local therapy in the opinion of investigator are eligible; for subjects with untreated asymptomatic CNS lesions > 2.0 cm magnetic resonance imaging (MRI), discussion with and approval from the lead principle investigator (PI) is required prior to enrollment\r\n* Subjects with stable brain metastases previously treated with radiation therapy or surgery are allowed to enroll, provided that they are off corticosteroids or on stable/tapering dose of corticosteroids and stability of CNS metastatic disease for at least 4 weeks has been demonstrated, with the last MRI taken within 2 weeks prior to cycle 1 day 1 of the study; relevant records of any CNS treatment must be available to allow for classification of target and non-target lesionsXx_NEWLINE_xXKnown CNS involvement of indolent lymphomaXx_NEWLINE_xXNo active CNS diseaseXx_NEWLINE_xXKnown or clinically suspected CNS involvementXx_NEWLINE_xXAny eligible histologic diagnosis other than desmoplastic medulloblastoma, with no evidence of CNS metastasisXx_NEWLINE_xXAny eligible histologic diagnosis, with evidence of CNS metastasisXx_NEWLINE_xXUntreated central nervous system (CNS) metastases or CNS metastases that have progressed after completion of radiotherapy.Xx_NEWLINE_xXPatients with asymptomatic treated CNS metastasis may be enrolled after discussion with the Medical Monitor.Xx_NEWLINE_xXActive, untreated CNS metastases.Xx_NEWLINE_xXSubjects with radiographic evidence of central nervous system (CNS) metastases as assessed by computerized tomography (CT) or magnetic resonance imaging (MRI) that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [e.g., dexamethasone]). Note: Subjects with CNS metastases are permitted to participate in the study if the CNS metastases are medically well controlled prior to screening (as assessed by the Investigator) after receiving local therapy (irradiation, surgery, etc.)Xx_NEWLINE_xXActive central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; prophylactic intrathecal medication is not a reason for exclusionXx_NEWLINE_xXPatients with metastatic to CNS with only cerebral spinal fluid (CSF) involvement are NOT ELIGIBLEXx_NEWLINE_xXPatients may have CNS 1, 2 or 3 disease.Xx_NEWLINE_xXPatients may have CNS 1 or CNS 2 disease but not CNS 3.Xx_NEWLINE_xXParticipants with untreated CNS metastases are excludedXx_NEWLINE_xXPatients with asymptomatic CNS metastases are allowedXx_NEWLINE_xXKnown primary central nervous system (CNS) malignancy or symptomatic or untreated CNS metastases. Treated and stable CNS metastases are allowed.Xx_NEWLINE_xXPatients with untreated (primary) or symptomatic CNS (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.Xx_NEWLINE_xXSubject has symptomatic central nervous system (CNS) metastasis. Subjects with asymptomatic, untreated CNS metastases are allowed. Subjects with previously treated and currently asymptomatic CNS metastases are eligible provided they meet the following:Xx_NEWLINE_xXKnown or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 daysXx_NEWLINE_xXSubjects with symptomatic or unstable CNS metastasesXx_NEWLINE_xXKnown active central nervous system (CNS) metastases. Subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to study entry, defined as:Xx_NEWLINE_xXNo evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.Xx_NEWLINE_xXActive central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; prophylactic intrathecal medication is not a reason for exclusion; patients with known brain metastases should be excluded from this clinical trialXx_NEWLINE_xXPatients with tumor involvement of the Central Nervous System (CNS). SCLC patients with previously treated CNS lesions must have stable CNS disease for at least 4 weeksXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for more than 1 week within 6 months prior enrollmentXx_NEWLINE_xXUntreated central nervous system (CNS) metastatic disease as defined by:\r\n* Solid tumors: history of untreated metastatic CNS tumor involvement; extradural masses which have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible; patients with previous CNS tumor involvement are eligible IF the CNS tumor(s) has been treated and has been stable or resolving for at least 4 weeks; and if the patient does not currently require steroidsXx_NEWLINE_xXPatient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ? 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy;Xx_NEWLINE_xXPatients with clinically unstable central nervous system (CNS) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by magnetic resonance imaging [MRI] or computed tomography [CT] scan within 4 weeks of the first day of study defined treatment and have CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)Xx_NEWLINE_xXKnown, uncontrolled CNS metastasesXx_NEWLINE_xXSymptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1-2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 4 weeks have elapsed from the last scanXx_NEWLINE_xXEvidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participationXx_NEWLINE_xXPatients with uncontrolled CNS tumor metastatic involvementXx_NEWLINE_xXHave CNS lesions that are confirmed to be stable or regressing on imaging since the time of the last CNS treatment including the pre-treatment CT or MRI scan for this trial.Xx_NEWLINE_xXUntreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:\r\n* Presence of measurable or evaluable disease outside of the CNS;\r\n* Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study\r\n* Completion of radiotherapy >= 8 weeks prior to the screening radiographic study\r\n* Discontinuation of corticosteroids and anticonvulsants >= 4 weeks prior to the screening radiographic studyXx_NEWLINE_xXPatient with CNS involvement unless they are at least 4 weeks from prior therapy completion.Xx_NEWLINE_xXPatients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptomsXx_NEWLINE_xXKnown untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria:\r\n* Presence of measurable disease outside the CNS\r\n* No radiographic evidence of worsening upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\r\n* No history of intracranial hemorrhage or spinal cord hemorrhage\r\n* No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed)\r\n* Absence of leptomeningeal diseaseXx_NEWLINE_xXPatients with untreated central nervous system (CNS) metastases; patients with treated CNS metastases who are off steroids are eligibleXx_NEWLINE_xXUntreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:\r\n* Presence of measurable or evaluable disease outside of the CNS;\r\n* Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study;\r\n* Completion of radiotherapy >= 8 weeks prior to the screening radiographic study;\r\n* Discontinuation of corticosteroids and anticonvulsants >= 4 weeks prior to the screening radiographic studyXx_NEWLINE_xXSubjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastasesXx_NEWLINE_xXPatients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and is in remission; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the protocolXx_NEWLINE_xXUntreated or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases may be eligibleXx_NEWLINE_xXHave symptomatic CNS malignancy (with the exception of medulloblastoma) or metastasis.Xx_NEWLINE_xXPatient with active CNS disease.Xx_NEWLINE_xXCurrent CNS LeukemiaXx_NEWLINE_xXHave symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 28 days.Xx_NEWLINE_xXPatient has symptomatic brain metastases, ie, presence of neurological symptoms or requiring treatment with corticosteroids, or CNS leukemia.Xx_NEWLINE_xXUntreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastasesXx_NEWLINE_xXKnown clinically active CNS leukemiaXx_NEWLINE_xXLeptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks)Xx_NEWLINE_xXKnown, clinically suspected, or history of CNS tumor involvement.Xx_NEWLINE_xXSymptomatic or untreated central nervous system (CNS) metastases; patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: no evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy; no ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed; completed stereotactic radiation at least 1 week prior to cycle 1, day 1 or whole-brain radiation at least 2 weeks prior to cycle 1, day 1Xx_NEWLINE_xXA history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.Xx_NEWLINE_xXHas untreated or uncontrolled CNS metastases, including patients who require glucocorticoid therapy for CNS metastasesXx_NEWLINE_xXClinical evidence of active CNS leukemic involvementXx_NEWLINE_xXPatients has primary CNS tumor or CNS tumor involvementXx_NEWLINE_xXPatients with brain metastasis treated or untreated, or other CNS diseaseXx_NEWLINE_xXPatients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.Xx_NEWLINE_xXPersistent and/or recurrent cervical cancer o No CNS/spinal metastasesXx_NEWLINE_xXPatients with CNS 3 disease or symptomatic CNS diseaseXx_NEWLINE_xXSymptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal metastatic involvement, have completed previous therapy (including radiation and/ or surgery) at least 4 weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvementXx_NEWLINE_xXActive, untreated CNS metastasesXx_NEWLINE_xXActive ALL in the CNS or testesXx_NEWLINE_xXHas untreated or uncontrolled central nervous system (CNS) metastases, including patients who require glucocorticoid therapy for CNS metastasesXx_NEWLINE_xXSymptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone =< 2 mg once daily for at least 5 days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1 week at the time of study treatmentXx_NEWLINE_xXPatients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.Xx_NEWLINE_xXNo 'active' CNS metastases. Prior CNS metastases are allowed, provided adequate palliative therapy has been administered and CNS disease control has been established prior to study entry. • A brain MRI scan, ? 28 days from day 1, is requiredXx_NEWLINE_xXCNS metastases that are symptomatic and /or requiring steroids.Xx_NEWLINE_xXHistory of central nervous system (CNS) hemorrhage or thrombosis; patients with a history of CNS lymphomatous involvement are eligible only if their CNS disease is in remission at the time of study entryXx_NEWLINE_xXEvidence of current CNS involvement.Xx_NEWLINE_xXKnown, uncontrolled CNS metastases or primary CNS lymphomaXx_NEWLINE_xXSymptomatic or untreated central nervous system (CNS) metastatic disease. Patients with previously treated CNS metastatic disease which has been stable for at least 56 days are eligibleXx_NEWLINE_xXPatient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: \r\n* No evidence of new or enlarging CNS metastasis \r\n* Off steroids that are used to minimize surrounding brain edemaXx_NEWLINE_xXPatients with known CNS (or leptomeningeal) metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.Xx_NEWLINE_xXSymptomatic CNS diseaseXx_NEWLINE_xXSymptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not requiredXx_NEWLINE_xXClinical evidence of CNS involvement by lymphomaXx_NEWLINE_xXCNS metastases.Xx_NEWLINE_xXKnown or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease (controlled CNS metastases are allowed)Xx_NEWLINE_xXKnown primary CNS lymphomaXx_NEWLINE_xXKnown CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeksXx_NEWLINE_xXPrimary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)Xx_NEWLINE_xXSymptomatic CNS metastasesXx_NEWLINE_xXPatients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included.Xx_NEWLINE_xXPatients with asymptomatic central nervous system (CNS) metastases will be eligible; for patients that have undergone radiation therapy for their CNS metastases, a minimum of 14 days must elapse prior to study registration, and patients must have recovered from any adverse events related to radiotherapy with the exception of alopecia and grade 1 neuropathyXx_NEWLINE_xXPrimary central nervous system (CNS) malignancy or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)Xx_NEWLINE_xXPatients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trialXx_NEWLINE_xXPrimary CNS tumor or CNS tumor involvementXx_NEWLINE_xXNewly identified CNS malignancies or documented progression of CNS metastases; subjects will be allowed only if the CNS metastases have been adequately treated with radiotherapy or surgery. For subjects receiving steroid therapy please refer to Section 6.3 for allowed steroid maintenance therapy.Xx_NEWLINE_xXPresence of CNS involvement of leukemia. Patients with a history of CNS involvement may be considered after discussion with the Medical MonitorXx_NEWLINE_xXPresence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapyXx_NEWLINE_xXPresence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapyXx_NEWLINE_xXPatients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.Xx_NEWLINE_xXUntreated or active central nervous system (CNS) metastases. Patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: evaluable or measurable disease outside the CNS, radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study, and screening CNS radiographic study is >/= 8 weeks since completion of radiotherapy and >/= 4 weeks since the discontinuation of corticosteroids and anticonvulsantsXx_NEWLINE_xXHave symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days.Xx_NEWLINE_xXSymptomatic CNS metastasesXx_NEWLINE_xXSymptomatic CNS metastasesXx_NEWLINE_xXSymptomatic CNS metastasesXx_NEWLINE_xXHistologically or cytologically confirmed non-small cell lung cancer or other “platinum responsive malignancies”, including but not limited to: esophageal cancer, ovarian cancer, germ cell malignancies, transitional cell cancer, that are not curable with chemotherapy, surgery or radiotherapy; a tissue block, 10 unstained slides or fresh tissue biopsy is required; patients with central nervous system (CNS) metastases which are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off steroids; patients with asymptomatic lesions without significant edema and no evidence of shift are allowed to participate without prior CNS therapy; such patients are anticipated to receive specific CNS therapy after 2-4 courses of study therapyXx_NEWLINE_xXHistory or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis except for subjects who have previously treated CNS metastases (surgery with or without radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria:\r\n* Are asymptomatic and,\r\n* Have had no clinical evidence of active CNS metastases for >= 28 days prior to enrollment and,\r\n* Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)Xx_NEWLINE_xXPatients with a history of central nervous system (CNS) metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidence by stable clinical findings and stable radiographic findings for a period of 6 weeksXx_NEWLINE_xXPatients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeksXx_NEWLINE_xXPatients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeks (cohort 2)Xx_NEWLINE_xXHistory and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets;Xx_NEWLINE_xXIn patients with CNS tumors or known CNS metastases, evidence of intracranial or intratumoral hemorrhage of more than punctuate size and/or more than 3 foci of punctuate hemorrhage on baseline magnetic resonance imaging (MRI) obtained within 14 days prior to study registrationXx_NEWLINE_xXPatients may have had prior central nervous system (CNS) metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by computed tomography [CT] or magnetic resonance imaging [MRI])Xx_NEWLINE_xXCNS leukemia.Xx_NEWLINE_xXPatients who have untreated (primary) or uncontrolled Central Nervous System (CNS) (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.Xx_NEWLINE_xXClinical evidence of active CNS leukemic involvementXx_NEWLINE_xXPatients with a history of CNS (central nervous system) leukemia are eligible if they are not symptomatic from current CNS involvement; if there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordingly with intrathecal chemotherapy per the treating physicianXx_NEWLINE_xXIn the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of ponatinib administration will be at least 2 weeks for cytotoxic agents OR at least 5 half-lives for cytotoxic/non-cytotoxic agents; use of one dose of cytarabine (up to 2 g/m^2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first eight weeks on study therapy from the day of enrollment, either prior to or concomitantly with ponatinib administration initially to control the peripheral blast count; concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted; controlled CNS leukemia is defined by the absence of active clinical signs of CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous cerebrospinal fluid (CSF) evaluationsXx_NEWLINE_xXCentral nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 monthly time intervalXx_NEWLINE_xXPresence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery).Xx_NEWLINE_xXHave symptomatic central nervous system (CNS) malignancy or metastasis. Asymptomatic participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids to treat CNS metastasesXx_NEWLINE_xXSymptomatic CNS metastasesXx_NEWLINE_xXHistory of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for subjects with symptoms of CNS leukemia to rule out extramedullary CNS involvement;Xx_NEWLINE_xXHistory of CNS hemorrhage within 28 days of study entry. This criterion may be waived at the investigator's request if the CNS hemorrhage was asymptomatic, with approval of the Medical MonitorXx_NEWLINE_xXPatients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.Xx_NEWLINE_xXActive CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.Xx_NEWLINE_xXCNS lesions: A) Patients with CNS parenchymal or meningeal-based lesions that are present at study entry are NOT eligible due to concerns regarding toxicity attribution. B) Who have active CNS disease or a history of cranial irradiation are excluded due to concerns regarding toxicity attribution. Patients with previously treated leptomeningeal disease or brain metastases without evidence of remaining tumor by PET, MRI scan, or spinal fluid will be eligible; however such patients currently taking steroids as prophylaxis against seizures are not eligible.Xx_NEWLINE_xXPatients with primary central nervous system (CNS) tumor or CNS tumor involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is: \r\n* > 4 weeks from prior therapy completion (including radiation and/or surgery)\r\n* Clinically stable with respect to the CNS tumor at the time of study entry \r\n* Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement\r\n* Not receiving anti-convulsive medications (that were started for brain metastases)Xx_NEWLINE_xXHistory of central nervous system (CNS) disease, CNS radiation, intrathecal therapy, or CNS surgeryXx_NEWLINE_xXPatient has symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Patients who received prophylactic CNS treatment are eligibleXx_NEWLINE_xXPatients with active central nervous system (CNS) metastasis and/or carcinomatous meningitis; however, patients with CNS metastasis (except leptomeningeal disease) who have completed a therapy and are clinically stable for 3 weeks as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants may be eligibleXx_NEWLINE_xXSubjects with active CNS or cerebrospinal fluid (CSF) involvement by malignancyXx_NEWLINE_xXPatients must not have a history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasesXx_NEWLINE_xXKnown central nervous system (CNS) disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: measurable disease outside the CNS, only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord), no evidence of progression or hemorrhage after completion of CNS-directed therapy, no ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed), no stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomizationXx_NEWLINE_xXActive (i.e., symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible for the trial if: a. the metastases have been treated by surgery and/or radiotherapy, b. the subject is off corticosteroids (>10 mg/day) and is neurologically stable for at least 2 weeks prior to Screening. c. brain MRI completed within 3 months of Screening.Xx_NEWLINE_xXHave known active uncontrolled or symptomatic CNS metastasesXx_NEWLINE_xXHave symptomatic CNS metastasis. Patients with a history of CNS metastases who have been treated with whole brain irradiation must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable does of steroids for ? 4 weeks prior to enrollment.Xx_NEWLINE_xXParticipants with a history of CNS metastases are eligible provided they are stable and meet the criteria details in the protocol.Xx_NEWLINE_xXPatients who have a history of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, psychosis, or other significant CNS abnormalities; a history of treated CNS leukemia will be allowed if recent CNS studies confirm the absence of active CNS disease at the time of study entry (screening)Xx_NEWLINE_xXCNS leukemiaXx_NEWLINE_xXSubjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is clinical suspicion of CNS involvement by leukemia during screening.Xx_NEWLINE_xXSubjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroidsXx_NEWLINE_xXParticipants with treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: * Evaluable or measurable disease outside the CNS * No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal cord hemorrhage * No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed * No evidence of significant vasogenic edema * No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 * Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study * Screening CNS radiographic study >/=4 weeks since completion of radiotherapy or surgical resection and >/=2 weeks since discontinuation of corticosteroidsXx_NEWLINE_xXCNS tumor or clinically active brain metastases.Xx_NEWLINE_xXEvidence of progression of central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing.Xx_NEWLINE_xX