There is at least 1 metastatic site at one or more of the following sites: spine or non-spine bone and at maximum 5 sites can be treated on protocol A MRI of the spine is required within 10 days prior to or at least 10 days after surgery Pathologically proven metastatic solid tumor (non-hematologic malignancy) of the bone (spine or non-spine bone) Primary spine tumor Women with severe bone density issues/osteoporosis (defined as any medical treatment for osteoporosis, and/or a T-score of -2.5 or lower, and/or history of fracture of the hip or spine) Pts w/ osteopenia (T-score of -1 to -2.5 at L/R total hip, L/R femoral neck or lumbar spine [L1-L4]) eligible Radiation to spine/pelvis bone or chemoradiation to pelvic organs Osteoporosis (T-score of 12 Prior radiation to the index spine All patients must have a brain MRI with and without contrast (gadolinium) within 30 days prior to study enrollment; all patients with history of spinal or leptomeningeal disease and those patients with symptoms suspicious of spinal disease, must have a spine MRI with contrast (gadolinium) performed within 30 days prior to study enrollment; lumbar puncture is necessary if there is evidence of tumor dissemination on the MRI of spine Patients must have radiographic evidence of malignancy in the spine or cauda equina region (L2 to sacrum) which is suitable for radiation therapy Patients must not have received radiation therapy to more than 20% of hematopoiesis forming bones (spine, pelvis and proximal long bones) during lifetime Tumors arising in the skull and spine No evidence of metastatic disease in the brain, spine or cerebrospinal fluid (CSF); assessments must include magnetic resonance imaging (MRI) imaging of the brain and spine with and without contrast and a lumbar puncture for CSF cytology A MRI of the spine is required within 10 days prior to or at least 10 days after surgery Patients with instability of the spine requiring instrumentation as judged by a neurosurgeon are not eligible For stratum B, patients must have disseminated recurrent disease (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate cerebrospinal fluid (CSF) flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines; children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy All patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment; if surgical resection is performed, patients must have pre-operative and post-operative cranial MRI with and without gadolinium; the post-operative brain MRI should be obtained within 72 hours of surgery; if patient has a biopsy only, post-operative cranial MRI is recommended but not required; all patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment; Note: if the spine study is performed for the first time after surgical resection or biopsy, it is recommended to be obtained with and without gadolinium Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium and spine are not eligible Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment Patients with disseminated disease to the spine are not eligible, and MRI of spine must be performed prior to enrollment if the treating physician suspects disseminated disease. Prior radiation or radiosurgery to the involved level of the spine Spine disease from leukemia, lymphoma or myeloma Patient with >= 1 asymptomatic spinal metastases of the thoracic spine OR >= 1 asymptomatic spinal metastases of the lumbar spine may be included; patients with spinal metastases to multiple vertebral levels may be included at the discretion of the investigator; however, only one vertebral level will be treated Patients with lesions in the upper cervical spine (C1-C5) or cervicothoracic junction (C6-T3) Prior irradiation of the spine site and level to be treated Pathological diagnosis of chondrosarcoma of the spine or sacrum or chordoma of the spine, or sacrum SPINE AND PARASPINAL LESIONS: Patients with disseminated intrinsic diffuse brainstem gliomas in either brain or spine; spine MRI should be performed prior to biopsy if clinically indicated Index vertebra(e) had previous spine surgery including vertebroplasty or kyphoplasty, Major surgery of the spine in same region as the index vertebra(e) was performed within 3 months before enrollment, Major elective surgery to the spine in same region as the index vertebra(e) is planned within 1 month following the ablation and cement procedure, If the index tumor is in the spine, there must be an intact cortex between the mass and the spinal canal and exiting nerve roots Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan Osteolysis of a vertebral body(ies) with or without fracture at a site of metastatic infiltration/multiple myeloma, that poses risk of impending vertebral collapse; this is detected by the following cross-sectional imaging (MRI or CT) conditions:\r\n* In the thoracic spine: \r\n** A >= 50% involvement of the vertebral body with no destruction of other structures or;\r\n** A >= 25% involvement of the vertebral body associated with costovertebral joint destruction or posterior elements involvement\r\n* In the lumbar spine: \r\n** A >= 35% involvement of the vertebral body with no destruction of other structures or;\r\n** A >= 20% involvement of the vertebral body associated with involvement of posterior elements In the investigator's judgment, focal neurologic deficit as a result of metastases in the brain, spine, or other central nervous system disorders. Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan Minimal volume, non-disseminated disease, defined by the following: \r\n* Residual tumor ? 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery\r\n* No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following: \r\n** Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery\r\n** Negative cytological examination of CSF after surgery, but before study enrollment History of a primary bone malignancy involving the lumbar spine Clinically significant fractures as defined by International Society for Clinical Densitometry (ISCD) (a long bone fracture of the lower extremities, vertebral compression fracture, or two or more long bone fractures of the upper extremities) indicated by a cast or a spine x-ray within the last 2 weeks History of prior trauma or orthopedic surgery to the cervical vertebral column/spine All patients must have histologic proof of solid tumor malignancy and radiographic evidence of spine metastasis All patients must have a single fraction spine radiosurgery at the designated site of interest to at least a dose of 18 Gray (Gy) All patients must be deemed at \high risk\ of developing vertebral body fracture by having at least one of the following characteristics: \r\n* Spine Instability Neoplastic Score classification of \Indeterminate\ deemed as a score from 7 to 12\r\n* Pre-existing vertebral body fracture\r\n* Planned radiation dose of 24 Gy Patients who have had prior radiotherapy at the spine site and level to be treated Patients who have had prior surgery at the spine level to be treated to include prior cement augmentation, laminectomy, vertebrectomy, tumor debulking, instrumentation The patient must have localized spine metastasis from the cervical (C)1 to lumbar (L)5 levels by a screening imaging study (bone scan, positron emission tomography [PET], computed tomography [CT], or MRI) (a solitary spine metastasis; two separate spine levels; or up to 3 separate sites [e.g., C5, thoracic (T)5-6, and T12] are permitted;) each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies; patients can have other visceral metastasis, and radioresistant tumors (including soft tissue sarcomas, melanomas, and renal cell carcinomas) are eligible Eligible metastatic lesions: 1) a solitary spine metastasis; 2) two contiguous spine levels involved; or 3) a maximum of 3 separate sites; each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies; epidural compression (arrow) is eligible when there is a >= 3 mm gap between the spinal cord and the edge of the epidural lesion; a paraspinal mass =< 5 cm is allowed There can be multiple small metastatic lesions shown in other vertebral bodies; the metastatic lesion of each spine should be less than 20% of the vertebral body as opposed to the diffuse vertebral involvement; these small lesions are often seen in the MRI even when bone scan or PET was negative; most of these lesions are not clinically required to be treated and are therefore not included in the target volume of this protocol; only the painful spine (pain score >= 5) is to be treated Patients with a paraspinal mass =< 5 cm in the greatest dimension and that is contiguous with spine metastasis are eligible Spine instability due to a compression fracture Prior radiation to the index spine Patients for whom an MRI of the spine is medically contraindicated History of severe osteoporosis (T score =< -4 either spine or hip), or presence of vertebral fracture Women with known osteoporosis or history of osteoporotic (fragility) fracture of the spine Osteoporosis: patients with a history of fragility fracture, or a hip or spine T score of < -2.5 (these patients will be treated with zoledronic acid and followed, but excluded from randomization) Tumors near critical structures such as those located near or in the brain or spine. This assessment will be determined by the treating clinician. Patients 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 damage Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar puncture\r\n* Note: lumbar puncture can be performed at the time of diagnosis and does not need to be repeated unless there is a change in neurological status or it was performed more than 14 days prior to study entry Patient does not have any documented history of central nervous system (CNS) involvement by mantle cell lymphoma; this includes no evidence of parenchymal brain, spinal cord, or cerebrospinal fluid involvement; radiculopathy symptoms from nerve root compression by lymphoma do not constitute CNS involvement NOTE: A lumbar puncture is not required in order to be enrolled on study nor are lumbar punctures recommended at the time of diagnosis; if the diagnosis of APL is known or suspected, diagnostic lumbar punctures in patients with neurologic symptoms should be deferred until any coagulopathy is corrected; if central nervous system (CNS) disease is suspected or proven, a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma; if CNS disease is documented, patients are still eligible and will receive protocol directed intrathecal treatments Patients 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 study Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement (no lumbar puncture required, clinical assessment per investigator’s judgment is sufficient) Patients 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 required Subjects with known active or history of CNS involvement by malignancy Patients with known involvement of the CNS by malignancy will be included if there is no evidence of active bleeding or intratumoral hemorrhage on radiographic imaging Patients with asymptomatic CNS involvement are allowed. Symptomatic CNS involvement. Known CNS involvement at diagnosis Symptomatic central nervous system (CNS) involvement or lymphangitic metastasis. Stable or improving CNS disease that is not under active treatment after receipt of adequate therapy is allowed. Leptomeningeal disease as the only site of CNS involvement Active involvement of the central nervous system (CNS) by lymphoma; work-up for CNS involvement at diagnosis will be directed as per the treating physician and will depend on specific clinical circumstances (no brain imaging or lumbar puncture is required by this protocol) Patients with metabolic storage diseases who have severe central nervous system (CNS) involvement of disease, defined as intelligence quotient (IQ) score < 70 Subject 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. Active CNS involvement Patients with known involvement of the CNS by malignancy will be excluded. Central Nervous System (CNS) involvement with multiple myeloma defined as csf positivity for plasma cells or a parenchymal CNS plasmacytoma Evidence of CNS involvement by NHL Known 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 imaging Active CNS involvement of their malignancy. Active central nervous system (CNS) involvement by malignancy, except in cases of virus-associated malignancies with CNS involvement in which case the patient may benefit from the transplant to control the malignancy Active CNS involvement by malignant cells (? 2 months from the conditioning) CNS metastatic involvement Known 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 investigator Known 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 involvement Known clinically active CNS involvement. Active central nervous system (CNS) involvement of leukemia (lumbar puncture not required to rule out CNS involvement if not suspected) Subjects with CNS involvement may be included on the study as long as they have not had any seizure activity in past 4 weeks CNS involvement with disease refractory to intrathecal chemotherapy Has 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 symptoms Prior or active central nervous system (CNS) involvement by myeloma (eg leptomeningeal disease); screening for this, for example, by lumbar puncture, is only required if suspicious symptoms or radiographic findings are present Absence of active central nervous system (CNS) involvement; NOTE: pre-enrollment lumbar puncture not mandatory Active 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) Patients 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 damage Known cytopathologically confirmed central nervous system (CNS) infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) CNS involvement with malignancy. Have prior or active central nervous system (CNS) involvement (e.g. leptomeningeal disease, parenchymal masses) with myeloma; screening for this (e.g. with lumbar puncture) is not required unless suspicious symptoms are present Patients diagnosed with primary central nervous system (CNS) or with CNS metastases/involvement, at any time during the disease course, are excluded from the study. Has 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 treatment Patients with metastatic central nervous system (CNS) tumors are allowed provided that they are clinically stable for a period of 30 days prior to study entry and there is not a requirement for steroid (other than close to physiologic doses) or anti-convulsant therapy; patients with leptomeningeal involvement are excluded Subjects 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 imaging 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 imaging For 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 imaging Clinical evidence of (parenchymal or meningeal) central nervous system (CNS) involvement or metastasis; in subjects suspected of having CNS disease, a magnetic resonance imaging (MRI) scan of the brain and lumbar puncture should be done to confirm Active 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 Gy Patients with active central nervous system (CNS) involvement with malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment Subjects with signs or symptoms indicative of CNS involvement; a CNS evaluation should be performed as clinically appropriate to rule our CNS involvement Subjects must not have prior or active central nervous system (CNS) involvement (e.g. leptomeningeal disease, parenchymal masses) with myeloma; screening for this (e.g. with lumbar puncture) is not required unless suspicious symptoms are present History of CNS involvement by MM Current CNS involvement by disease Active central nervous system (CNS) involvement by malignancy; Note: Patients with history of CNS disease that has been effectively treated will be eligible provided that treatment was > 4 weeks before enrollment Patients with active central nervous system (CNS) involvement by malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment Skin involvement. Participants with known central nervous system (CNS) involvement with leukemia or who are receiving intrathecal chemotherapy that is either prophylactic or therapeutic; history of CNS involvement that has been completely treated (no longer receiving intrathecal chemotherapy) will be allowed Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning (day -6) Evidence for active CNS involvement by leukaemia Patients diagnosed with primary central nervous system (CNS) or with CNS metastases or involvement, at any time during the disease course, are excluded from the study. Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative computed tomography (CT) scan or negative diagnostic lumbar puncture prior to first dose 210 Evidence of CNS involvement by NHL. Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study) Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy; diagnostic lumbar puncture is to be performed Patient has a known or suspected primary central nervous system (CNS) tumor or CNS tumor involvement or active leptomeningeal disease. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) Patients with suspected central nervous system (CNS) involvement should undergo lumbar puncture; those with documented CNS involvement will be excluded Patients 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 enrollment Central nervous system involvement; a lumbar puncture does not need to be performed unless there is clinical suspicion of leptomeningeal disease With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy, cranial irradiation or both prior to initiating conditioning (day -6) Patients with metabolic storage diseases who have severe central nervous system (CNS) involvement of disease, defined as intelligence quotient (IQ) score < 70 History of known leptomeningeal involvement (lumbar puncture not required) Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma \r\n* Any laboratory or radiographic tests performed to assess CNS involvement must be negative and must be performed within 42 days prior to registration Patients 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. Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines. Active signs or symptoms of CNS involvement by malignancy Patients with primary CNS tumor or CNS tumor involvement Evidence of CNS involvement with DLBCL CNS lymphoma involvement A 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. Patients 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 treatment History 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) Patients with active central nervous system (CNS) involvement by malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment Participants with active central nervous system (CNS) involvement are excluded; patients with suspected CNS disease should be worked up appropriately prior to enrollment Primary CNS lymphoma or evidence of CNS involvement by lymphoma Known central nervous system lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL Subjects 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. Patients 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 accordingly Patients with active central nervous system (CNS) involvement with malignancy; patients with prior CNS disease that has been effectively treated will be eligible providing treatment was > 4 weeks before enrollment Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukaemic CNS involvement (no lumbar puncture required, clinical assessment per investigator´s judgement is sufficient). Absence of CNS involvement by leukemia. Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic lumbar puncture is to be performed per protocol Untreated central nervous system (CNS) involvement; (treated CNS involvement is permitted only if the patient is not currently on steroid therapy or has remained on a stable, unchanged dose of steroid for >= 2 weeks) Known cytopathologically confirmed central nervous system (CNS) infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) Known active CNS involvement Known CNS involvement of indolent lymphoma Known or clinically suspected CNS involvement Symptomatic CNS involvement (other than signs and symptoms caused by leptomeningeal disease) Active central nervous system (CNS) involvement by malignancy (defined as CNS-3 per National Comprehensive Cancer Network [NCCN] guidelines) CNS or leptomeningeal involvement of lymphoma Known Central Nervous System (CNS) lymphoma; subjects with symptoms of CNS disease must have a negative CT scan and negative diagnostic lumbar puncture Patients 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 weeks Known active and uncontrolled central nervous system (CNS) involvement of leukemia (a lumbar puncture does not need to be performed as a part of screening) Untreated 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 steroids Patients with uncontrolled CNS tumor metastatic involvement Known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging; a lumbar puncture is not required unless CNS involvement is clinically suspected; patients with signs or symptoms of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion. Patients 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 protocol Known, clinically suspected, or history of CNS tumor involvement. Patients with known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging; a lumbar puncture is not required unless CNS involvement is clinically suspected; patients with signs or symptoms of leukemic meningitis or a history of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment Patients has primary CNS tumor or CNS tumor involvement Symptomatic 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 involvement Patients 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. Evidence of current CNS involvement. Patients 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. Clinical evidence of CNS involvement by lymphoma Primary CNS tumor or CNS tumor involvement Recipient must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous CNS tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain. Presence of CNS involvement of leukemia. Patients with a history of CNS involvement may be considered after discussion with the Medical Monitor Presence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapy Presence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapy The patient was diagnosed with leukemic Central Nervous System (CNS) disease (e.g. before chemotherapy) or presents neurological symptoms at baseline suggestive of a CNS involvement. Prior central nervous system (CNS) involvement by tumor is permissible if previously treated and clinically stable for two weeks after completion of treatment. Patients 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 physician History 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; Active 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. Patients with history of John Cunningham (JC) virus identified in the cerebrospinal fluid (CSF) or previous history of PML will be excluded from the study Patient must be CNS (cerebrospinal fluid [CSF]) negative for leukemia Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL ELIGIBILITY 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 allowed ELIGIBILITY 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 allowed Positive cerebrospinal fluid (CSF) cytology during staging, symptomatic leptomeningeal involvement, or parenchymal involvement of brain or spinal cord Clinical evidence suggestive of central nervous system (CNS) involvement with MDS unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF) Central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF) evaluation Lesions on imaging, by cerebrospinal fluid or with neurological findings that are consistent with leptomeningeal disease or meningeal carcinomatosis. Patients with leptomeningeal disease (leptomeningeal enhancement on MRI/CT imaging and/or positive cerebrospinal fluid [CSF] cytology) are not eligible to enroll Central nervous system (CNS) leukemia (including leukemia detectable in the cerebrospinal fluid and/or solid chloromas) refractory to intrathecal chemotherapy and/or craniospinal radiation Has evidence of leptomeningeal disease on MRI or in cerebrospinal fluid (CSF) Known active central nervous system metastases and/or lymphomatous meningitis; patients with isolated cerebrospinal fluid (CSF) involvement detectable by flow cytometry are eligible if clinically asymptomatic and if abnormal B cells are reported to be less than 3% by flow cytometry; subjects with previously treated central nervous system (CNS) disease may participate provided: 1) any CNS-directed treatment was completed at least 1 month prior to enrollment, 2) imaging studies and CSF evaluation show no evidence of disease progression, and 3) any neurologic symptoms have returned to baseline Patients 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) Patients with diffuse subependymal or cerebrospinal fluid (CSF) disease Patients with known brain, spinal or cerebrospinal fluid (CSF) involvement are excluded\r\n* Prophylactic intrathecal therapy is allowed per institutional protocol if deemed necessary Known central nervous system (CNS) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that have been effectively treated to complete remission (< 5 white blood cell [WBC]/mm^3 and no blasts in cerebrospinal fluid [CSF]) will be eligible. Known active DLBCL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis). Patients with known central nervous system (CNS) involvement with AML are eligible provided that they have been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment A history of AML related central nervous system (CNS) involvement is allowed if most recent cerebrospinal fluid (CSF) analysis is negative at least 2 weeks prior to study treatment Patients with current central nervous system (CNS) involvement by malignancy (either by imaging or cerebrospinal fluid involvement or biopsy-proven) Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases. Has carcinomatous meningitis as determined by positive cerebrospinal fluid (CSF) cytology Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 2 consecutive documented, negative spinal fluid assessment prior to Screening Active ALL in the central nervous system (CNS), as defined by >= 5 leukocytes per microL with identifiable blast cells in the cerebrospinal fluid (CSF), and/or the presence of cranial-nerve palsies Patients with known central nervous system (CNS) involvement with AML are eligible provided that they have been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 1 documented, negative spinal fluid assessment within 28 days prior to Screening Magnetic resonance (MR) imaging of the brain (performed within 14 days of enrollment) must demonstrates no evidence of diffuse leptomeningeal spread beyond the primary relapse site in posterior fossa and no obstruction of cerebrospinal fluid flow (CSF) Has known active central nervous system (CNS) leukemia and/or leukemic meningitis; subjects with previously treated CNS leukemia may participate provided they are stable (e.g., without evidence of active disease by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline) and have no evidence of leukemic blasts on analysis of cerebrospinal fluid (CSF) In patients with suspected leptomeningeal disease, the diagnosis of leptomeningeal disease should be confirmed by the presence of neurological or imaging signs and/or positive cerebrospinal fluid (CSF) cytology Patients with current central nervous system (CNS) involvement by malignancy (either by imaging or cerebrospinal fluid involvement or biopsy-proven) Absolute neutrophil count (ANC) >= 1500/uL, without cerebrospinal fluid (CSF) support Patients with >= 5 white blood cells in the cerebrospinal fluid with blasts (CNS3) disease will be eligible if central nervous system (CNS) disease is responsive to therapy Patients 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) discretion Diffuse subependymal or cerebrospinal fluid (CSF) disease Presence of active central nervous system (CNS) leukemia - cerebrospinal fluid (CSF) with < 5 white blood count (WBC)/uL will not exclude the patient Active central nervous system (CNS) involvement by malignancy (patients with known positive cerebrospinal fluid [CSF] cytology or parenchymal lesions visible by computed tomography [CT] or magnetic resonance imaging [MRI]) Patients with known central nervous system (CNS) involvement with AML are eligible provided that they have been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment into the study; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment RECIPIENT: Active central nervous system (CNS) involvement by malignancy (patients with known positive cerebrospinal fluid [CSF] cytology or parenchymal lesions visible by computed tomography [CT] or magnetic resonance imaging [MRI]) Active involvement of the central nervous system with malignancy; this can be documented as a normal neurological exam and/or a negative cerebrospinal fluid (CSF) analysis Patients will be excluded if there is radiographic or cerebrospinal fluid (CSF) cytological evidence of leptomeningeal disease Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of treatment; prophylactic intrathecal medication is not a reason for exclusion Active central nervous system (CNS) involvement by malignancy (patients with known positive cerebrospinal fluid [CSF] cytology or parenchymal lesions visible by computed tomography [CT] or magnetic resonance imaging [MRI]); except in the case of viral associated malignancies in which case the patient may benefit from the transplant to control the malignancy Active cerebrospinal fluid involvement with malignancy or brain metastasis Patients 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 required Has active central nervous system (CNS) involvement (documented by radiologic lesions and/or malignant cells in the cerebrospinal fluid [CSF]). Patients are excluded if there is radiographic or cerebrospinal fluid (CSF) evidence of leptomeningeal disease. Patients must have histological verification of diagnosis. Patients with M+ disease (defined as evidence of neuraxis dissemination) are not eligible. Cerebrospinal fluid (CSF) cytology is not required but may be obtained if clinically indicated prior to study enrollment. If cytology is positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible Active 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) Active central nervous system (CNS) disease – if a history of AML related CNS involvement, screening cerebrospinal fluid (CSF) analysis must be negative Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology High-risk medulloblastoma defined by any of the following:\r\n* > 1.5 cm^2 residual disease for any medulloblastoma histology, or\r\n* Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery unless contraindicated, or\r\n* Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or\r\n* M4 disease Active central nervous system (CNS) lymphoma, history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; patients with a history of positive cerebrospinal fluid cytology that has become negative with intrathecal chemotherapy and the patient has been in remission for at least 12 months are eligible Patients with a history of central nervous system (CNS) leukemia must be stable, off steroids, with clear cerebrospinal fluid (CSF) for > 3 months prior to day 1 of Erwinaze administration (patient can receive monthly intrathecal maintenance chemotherapy) Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF) evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or malignant cells identified on cerebrospinal fluid [CSF] cytology) are excluded Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology Known 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. The 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. No 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 form EXCLUSION FOR TREATMENT: Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of treatment; prophylactic intrathecal medication is not a reason for exclusion\r\n* If the lumbar puncture (LP) is traumatic (containing red blood cells [RBCs]) and cannot be repeated the Steinherz/Bleyer ratio will be used to determined unequivocal evidence of CSF leukemia at the discretion of the treating physician STRATUM I:\r\n* Minimal disseminated disease (MDD) < 1% at diagnosis in T-lymphoblastic lymphoma (TLL)\r\n* No bone marrow involvement microscopically at diagnosis in B-lymphoblastic lymphoma \r\n* Patients should NOT have: \r\n** Any CNS involvement: CNS-3 status (i.e., >= 5 white blood cell [WBC]/uL of cerebrospinal fluid [CSF] with blasts or cranial nerve palsy), CNS-2 status (< 5 WBC/uL of CSF with blasts) or traumatic lumbar puncture (LP) (> 10 red blood cell [RBC]/uL of CSF with blasts) \r\n** Overt testicular involvement (evidenced by ultrasonogram) For Primary Central Nervous System (CNS) Lymphoma (PCNSL): Subjects must have disease that is objectively measurable by International Workshop to Standardize Baseline Evaluation and Response Criteria in Primary CNS Lymphoma, Cerebrospinal Fluid (CSF) cytology (in case of leptomeningeal only disease), or vitreal aspiration cytology and/or retinal photographs (in case of ocular lymphoma). Recurrent/refractory CNS non-Hodgkin's lymphoma involving CNS (Brain, Cerebrospinal fluid (CSF) or intraocular compartments) Patients with central nervous system (CNS) leukemia are eligible as long as they have received treatment and most recent cerebrospinal fluid (CSF) analysis is negative for leukemia Have active leukemic central nervous system (CNS) involvement, as defined by any leukemic blasts detected in the cerebrospinal fluid (CSF) by morphology or flow cytometry and/or any chloromas detected by CNS imaging Patients may not have a known history of leptomeningeal disease, as diagnosed by positive cerebrospinal fluid (CSF) cytology, unless prospective permission for enrollment is granted from the sponsor and the PI Diffuse subependymal or cerebral spinal fluid (CSF) disease Tumor involving both hemispheres or that which involves the subependyma or suspected cerebrospinal fluid dissemination Absolute neutrophil count (ANC) >= 1500/uL, without cerebrospinal fluid (CSF) support Patients with infratentorial, multifocal, or pathologically confirmed cerebrospinal fluid (CSF) disseminated tumor Diagnosis of primary central nervous system (CNS) diffuse large B-cell lymphoma confirmed by one of the following:\r\n* Brain biopsy or resection\r\n* Cerebrospinal fluid\r\n* Vitreous fluid Known leptomeningeal or parenchymal brain involvement with lymphoma unless in complete remission after treatment for at least 12 weeks with negative cerebrospinal fluid (CSF) cytology within 2 weeks; prophylaxis of central nervous system (CNS) disease using intrathecal or intraventricular dosing of cytotoxic regimens is permitted and should be performed according to the discretion of the treating physician Active central nervous system (CNS) malignancy; however, patients with a history of positive Cerebrospinal fluid (CSF) cytology that has become negative with intrathecal chemotherapy are eligible. Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment Patients with known prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology; NOTE: discrete dural metastases are permitted Participants must have histologically confirmed germ cell tumor or elevated alpha-fetoprotein (AFP) (serum > 10 IU/L or cerebrospinal fluid [CSF] > than institutional norm) or beta-human chorionic gonadotropin (B-HCG) (serum or CSF > than institutional norm) in the setting of radiographic disease consistent with a germ cell tumor; disease must be confined to the central nervous system Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of enrollment; prophylactic intrathecal medication is not a reason for exclusion Patients with active brain metastases, or with a history of any central nervous system (CNS) metastases or cerebrospinal fluid malignant cells\r\n* Note: patients who are asymptomatic but are found to have malignant cells in the cerebrospinal fluid (CSF) on lumbar puncture prior to treatment will be considered eligible Active central nervous system (CNS) involvement by malignancy (patients with known positive cerebrospinal fluid [CSF] cytology or parenchymal lesions visible by computed tomography [CT] or magnetic resonance imaging [MRI]) 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; prophylactic intrathecal medication is not a reason for exclusion Patients with metastatic to CNS with only cerebral spinal fluid (CSF) involvement are NOT ELIGIBLE 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; prophylactic intrathecal medication is not a reason for exclusion; patients with known brain metastases should be excluded from this clinical trial Cerebrospinal fluid (CSF) cytology for lymphoma or monoclonal lymphocyte population as defined by cell surface markers. CD20+ B-cell primary central nervous system lymphoma (PCNSL) confirmed at the time of diagnosis by histology, cytology, or immunocytochemistry from cerebrospinal fluid (CSF); diagnosis must be documented by pathology report Subjects 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 metastases Patients must have primary brain malignancy (histologically confirmed by surgical specimen or cerebral spinal fluid [CSF] cytology), or metastatic brain malignancy; if the patient has metastatic brain malignancy, there must be a histologic pathology report confirming the primary site of the cancer, as well as one of the following: confirmation by surgical specimen, CSF cytology, elevated tumor markers, or clinical evidence of CNS involvement Evidence of leptomeningeal disease by MRI and/or cerebrospinal fluid (CSF) cytology Central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy History of seizures, elevated intracranial pressure (ICP) or cerebrospinal fluid (CSF) obstructive states (e.g. severe head injury, central congenital or mass lesions) Patients who are not a candidate for intrathecal drug therapy due to coagulopathy, concurrent necessary use of blood thinners, presence of systemic infection, drug allergy to analgesic agent, evidence of cerebrospinal fluid (CSF) obstruction or other technical factor Subjects with active CNS or cerebrospinal fluid (CSF) involvement by malignancy Immunocompetent patients with newly diagnosed or recurrent non-Hodgkins lymphoma involving the brain (primary or secondary), as demonstrated by magnetic resonance imaging (MRI) and histologic confirmation either by positive cerebrospinal fluid (CSF) cytology for lymphoma or a monoclonal lymphocyte population defined by cell surface markers, vitreous or uvea biopsy or brain biopsy Participants with glioblastoma involving the brainstem or posterior fossa, cerebrospinal fluid dissemination Presence of radiographically suspected leptomeningeal disease (LM) or carcinomatous meningitis (CM) AND/OR presence of at least one CNS lesion for which the following criteria are met:\r\n* For patients without leptomeningeal disease: presence of at least one parenchymal CNS lesion that is at least 5 mm in size; Note: intra-cranial disease assessments can only be performed using contrast-enhanced magnetic resonance imaging (MRI); MRI scan slices of 1 mm are necessary for brain metastases between 5 and 10 mm in size\r\n* The lesion(s) must be newly diagnosed or be present as progression after local therapy, including surgery and/or radiation therapy; for patients who have received local therapy, progression of pre-existing lesions based on RECIST v1.1 (> 20% increase in longest diameter on baseline scan) or new lesions are required\r\n* Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to the first dose of study treatment\r\n* For patients with suspected LM or CM based on imaging, spinal fluid sampling for confirmation is not required; for patients who do undergo spinal fluid sampling, those with negative spinal fluid (CSF) are eligible to enter Subjects with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases Patients must not have clinical evidence of central nervous system involvement by lymphoma; if performed, any laboratory or radiographic tests performed to assess central nervous system (CNS) involvement must be negative Symptomatic or progressing or steroid requiring Central Nervous System (CNS) involvement disease at least four weeks prior to randomization Known central nervous system (CNS) involvement Patients with a known central nervous system (CNS) involvement of lymphoma are not eligible (CNS staging not required) Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Current or past history of central nervous system (CNS) disease, or CNS involvement by MM Central nervous system (CNS) involvement Patients with known central nervous system (CNS) involvement of lymphoma are not eligible Evidence of leukemic meningitis or other central nervous system (CNS) involvement by leukemia Patients must not have known central nervous system (CNS) involvement of lymphoma Has clinical signs of central nervous system (CNS) involvement of MM. Known central nervous system (CNS) involvement by lymphoma Central nervous system (CNS) involvement by lymphoma/leukemia Known central nervous system (CNS) involvement by malignancy Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation Known central nervous system (CNS) involvement with CLL or T-LGL Prior central nervous system (CNS) involvement by tumor cells; Known central nervous system (CNS) involvement Patients with history of central nervous system (CNS) involvement Known central nervous system (CNS) involvement The toxicity profile of nivolumab in patients with disease involvement of the central nervous system (CNS) is unknown Known central nervous system (CNS) involvement by lymphoma Central nervous system (CNS) involvement, including lymphomatous meningitis Prior central nervous system (CNS) involvement by tumor cells Participant has known Central Nervous System (CNS) involvement with AML. History of plasma cell leukemia or multiple myeloma (MM) central nervous system (CNS) involvement Known central nervous system (CNS) involvement Central nervous system (CNS) involvement Uncontrolled central nervous system (CNS) involvement by tumor cells within the past 2 months Central nervous system (CNS) involvement by lymphoma Central nervous system (CNS) involvement Central nervous system (CNS) involvement by lymphoma (clinically or cytologically confirmed) Patients with known central nervous system (CNS) involvement Known brain metastases or central nervous system (CNS) involvement Known central nervous system (CNS) tumor involvement History of plasma cell leukemia or MM central nervous system (CNS) involvement Central nervous system (CNS) involvement Patients with history of extramedullary AML, except for central nervous system (CNS) involvement that is currently controlled, will not be eligible for enrollment Central nervous system (CNS) involvement within 3 months Patient must have no current or prior history of central nervous system (CNS) involvement Patients with known central nervous system (CNS) involvement Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Patients with known central nervous system (CNS) involvement by leukemia History of plasma cell leukemia or central nervous system (CNS) involvement Known central nervous system (CNS) involvement with lymphoma. Patient has distant metastatic disease, including central nervous system (CNS) tumor involvement Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria: Symptomatic central nervous system (CNS) involvement by AML Untreated central nervous system (CNS) involvement Uncontrolled central nervous system (CNS) disease involvement AML central nervous system (CNS) involvement Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy Patients must have no known central nervous system (CNS) involvement by lymphoma Central nervous system (CNS) involvement by lymphoma/leukemia Patients who have symptomatic central nervous system (CNS) involvement are not eligible Central nervous system (CNS) involvement. Patients with documented central nervous system (CNS) involvement Patient must have no known central nervous system (CNS) involvement Known central nervous system (CNS) involvement by malignancy Known central nervous system (CNS) involvement Symptomatic central nervous system (CNS) lymphoma involvement Subjects with known or suspected central nervous system (CNS) involvement are not eligible Patients with known central nervous system (CNS) involvement are excluded from this clinical trial Central nervous system (CNS) involvement by CLL. Research participants with known brain metastases (central nervous system [CNS] involvement either parenchymal or leptomeningeal involvement) Has evidence of uncontrolled central nervous system (CNS) involvement (previous radiation and off steroids is acceptable) Central nervous system (CNS) involvement by lymphoma Phase II: Patients with untreated, relapsed or refractory T-cell lymphoma, including patients with central nervous system (CNS) involvement or lymphomatous meningitis are allowed on study History of central nervous system (CNS) involvement by myeloma Known central nervous system (CNS) involvement of lymphoma Known central nervous system (CNS) involvement Central nervous system (CNS) involvement of the patient's lymphoma Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation Patients with central nervous system (CNS) involvement Known central nervous system (CNS) involvement Known central nervous system (CNS) involvement by lymphoma. Uncontrolled central nervous system (CNS) involvement with disease Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Known central nervous system (CNS) lymphoma involvement Evidence of AML central nervous system (CNS) involvement Central nervous system (CNS) involvement. Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy and/or standard cranial-spinal radiotherapy Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Patient has central nervous system metastatic involvement. Patients with previously treated CNS metastases are also excluded. Known central nervous system lymphoma or ALL with central nervous system (CNS) involvement Central nervous system (CNS) involvement of DLBCL Current central nervous system (CNS) involvement by lymphoma Known central nervous system (CNS) involvement Symptomatic central nervous system (CNS) involvement Symptomatic central nervous system (CNS) involvement Symptomatic, steroid-requiring or progressive central nervous system (CNS) involvement Clinically uncontrolled central nervous system (CNS) involvement Patients with central nervous system (CNS) metastatic involvement. Clinically uncontrolled central nervous system (CNS) involvement Patients must not have clinical evidence of central nervous system involvement by lymphoma, since proposed treatment would not be able to address it adequately; any laboratory (e.g., lactate dehydrogenase [LDH]) or radiographic tests performed to access central nervous system (CNS) involvement must be negative and must be performed within 42 days prior to registration Known central nervous system (CNS) involvement Known Central Nervous System (CNS) involvement by lymphoma. Presence of central nervous system (CNS) involvement with Hodgkin lymphoma Uncontrolled central nervous system (CNS) involvement by tumor cells Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma History of central nervous system (CNS) involvement Known presence of central nervous system (CNS) involvement by lymphoma Known central nervous system (CNS) involvement Patients with known central nervous system (CNS) involvement Participants with known central nervous system (CNS) involvement of lymphoma Known central nervous system (CNS) involvement Known central nervous system (CNS) involvement by AML Patients must not have known central nervous system (CNS) involvement Patients with known central nervous system (CNS) involvement Known central nervous system (CNS) involvement of lymphoma (CNS staging not required) Clinical signs of central nervous system (CNS) involvement of MM. Known evidence of active cerebral/meningeal CLL; patients may have a history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) Known evidence of active cerebral/meningeal CLL; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration Known 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 exclusion Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (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 that time of registration Known evidence of active cerebral/meningeal CLL; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration Clinical evidence of active CNS leukemic involvement Evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration Clinical evidence of active CNS leukemic involvement Known evidence of active cerebral/meningeal CLL; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration