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 corticosteroids
Patients 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 corticosteroids
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 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 corticosteroids
Patients 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 corticosteroids
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 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 corticosteroids
Participants 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 corticosteroid
Patients 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 treatment
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** 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 corticosteroids
If 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 scan
Known 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.
Known 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 disease
Active 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 corticosteroids
Known 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 corticosteroids
Known 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 corticosteroids
Known 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 corticosteroids
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 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 corticosteroids
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 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 corticosteroids
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 =< 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 corticosteroids
Known 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 corticosteroids
Participants 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 stability
Patients 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 1
Patients 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 corticosteroids
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 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 corticosteroids
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 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 study
Known 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 disease
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 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 study
Symptomatic 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 1
Untreated 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 anticonvulsants
Known 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 randomization
Participants 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 corticosteroids
Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, antibody based therapy, e.g. lapatinib, bevacizumab, erlotinib, imatinib, that are sometimes offered on a compassionate-use basis to NF2 patients)
Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm)
An optic pathway glioma
History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal metastatic disease; or intracranial hemorrhage Additional Exclusion Criteria:
May not have a NF1 related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy or surgery
Known ophthalmologic conditions, such as:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Tumors of all regions of the CNS, with appropriate histology are eligible for study; however patients with SEGA or tumors intrinsic to the optic nerve and involvement of the optic nerve that cannot be biopsied/resected are eligible without histological confirmation
Patient must have one of the following: \r\n* For stratum 5: non NF-1 associated low grade glioma (LGG) (other than pilocytic astrocytoma or optic pathway glioma) \r\n* For stratum 1 or 2: non NF-1, non-optic pathway pilocytic astrocytoma; note: all patients with non NF-1 associated optic pathway glioma with or without tissue must be enrolled on stratum 4
Patients with sporadic (non NF-1 associated), histologically diagnosed progressive, recurrent or refractory non-optic pathway pilocytic astrocytoma who have pre- treatment tumor tissue available for BRAF analysis
Patients with progressive, recurrent or refractory optic pathway glioma, with or without pre-treatment tumor tissue
Patients with histologically diagnosed progressive, recurrent or refractory non NF-1 associated LGG (other than pilocytic astrocytoma or optic pathway glioma); these patients must have BRAF aberrations as documented by the Lindeman and Ligon Labs at Brigham and Women’s Hospital using the same procedures
Patients will be assigned to one of 6 strata prior to enrollment; all BRAF assessments used for stratification below must be done at the Lindeman and Ligon Labs at Brigham and Women’s Hospital using the same procedures as described in this protocol; assessments for both BRAF V^600E mutation and BRAF KIAA1549 fusion are required for patients who will enroll on strata 1, 2 and 5 \r\n* Stratum 1: patients with non NF-1 associated progressive, recurrent or refractory pilocytic astrocytoma with pre-trial tumor material available and with a BRAF aberration i.e. BRAFV^600E mutation and/or BRAF KIAA1549 fusion as determined by IHC and FISH, respectively; patients with optic pathway glioma are excluded\r\n* Stratum 2: patients with non NF-1 associated progressive, recurrent or refractory pilocytic astrocytoma with pre-trial tumor material available and without a BRAF aberration i.e. BRAF^V600E mutation and/or BRAF KIAA1549 fusion as determined by IHC and FISH, respectively; patients with optic pathway glioma are excluded\r\n* Stratum 3: patients with neuro-fibromatosis 1 (NF-1) associated progressive, recurrent or refractory low grade glioma (World Health Organization [WHO] grade I & II), with or without tissue\r\n* Stratum 4*: patients with non-NF1 associated progressive, recurrent or refractory optic pathway glioma with or without tissue available for BRAF evaluation\r\n* Stratum 5: patients with non NF-1 associated progressive, recurrent or refractory low grade glioma other than pilocytic astrocytoma or optic pathway glioma with a documented BRAF aberration identified in pre-trial tumor material\r\n* Stratum 6: patients with non-NF-1 associated progressive, recurrent or refractory low grade glioma (other than optic pathway glioma [OPG]) with tissue available for BRAF analyses who cannot be classified into stratum 1, 2 or 5 due to inadequate tissue quality, assay failure, etc\r\n**Clarification: Stratum 4 was specifically designed for patients with hypothalamic/optic pathway gliomas; the intent is that if there is any optic chiasm invasion regardless of where the tumor is originating from (chiasm vs. hypothalamus vs. other location), the patient should be enrolled on Stratum 4, regardless of whether the tumor has been biopsied or not; obviously, there are some tumors that include part of the hypothalamus and clearly do NOT include the chiasm at all; in these situations, and if the tumor is a biopsy proven pilocytic astrocytoma, these patients should be enrolled on Stratum 1 or 2 (depending upon BRAF status)
Fiber optic exam with laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure) within 8 weeks prior to registration
Ophthalmological conditions as follows:\r\n* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion\r\n* Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)\r\n* Evidence of optic glioma, malignant glioma, malignant peripheral nerve sheath tumor,\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study\r\n* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility
Papilledema or other active optic nerve disorder
Metastases within 2 mm of the optic apparatus
May not have a NF1 related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy, radiation, or surgery
Known ophthalmologic conditions, such as:\r\n* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR)\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility \r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Lesion(s) involving the brainstem, optic chiasm or optic nerve(s)
Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts)
Previous pathologic confirmation of a tumor treated with radiation to the brain completed at least 6 months prior to the start of planned reirradiation, except for patients with tumors that are routinely diagnosed without biopsy, including germinoma and optic pathway glioma; patients with a history of cranial irradiation for leukemia are eligible
Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment
Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
Adjacent tumor location to optic apparatus or brainstem, precluding achievement of meaningful dose with SRS
Lesion located in anatomic regions that are not amenable to SRS, including the brain stem, optic apparatus, or eloquent cortex
At the time of planning, unable to deliver 10 Gray (Gy) or less to optic nerve/chiasm
Unable to deliver 10 gray (Gy) or less to optic nerve/chiasm (typically 3 mm or more separation of the tumor from the optic nerve/chiasm is necessary)
Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
Phase I: patients must have recurrent or refractory solid tumors or acute leukemia (limited to AML or ALL) or have been intolerant of prior therapies, confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), e.g., solid tumors including rhabdomyosarcoma, Ewing sarcoma, soft tissue sarcomas; these may include primary neoplasms of the central nervous system, such as high-grade (World Health Organization [WHO] grade III-IV) glioma; patients with diffuse intrinsic pontine glioma (DIPG) or optic pathway glioma are exempt from histologic verification; for DIPG typical magnetic resonance imaging (MRI) findings must be present which include hypo- or isointense on T1-weighted imaging, hyperintense on fluid attenuation inversion recovery (FLAIR) or T2-weighted imaging, epicenter in the pons in the face of a typical clinical presentation; optic pathway glioma are located in the optic pathway and are typically hypo- or iso-intense on T1 and hyperintense on T2-weighted images
Patients with known ophthalmologic conditions, such as:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or upper limit of normal [ULN] adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal plexiform neurofibroma (PN) (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Recurrent tumors near the brainstem and optic chiasm must not have received prior radiation therapy
Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic apparatus (optic nerves and chiasm)
No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm)
Recurrent tumors near the brainstem and optic chiasm must not have received prior radiation therapy
Patients with compression of the optic chiasm due to a macroadenoma or patients at high risk of compression of the optic chiasm (tumor within 2 mm of optic chiasm).
Subjects with glaucoma, intraocular pressure > 21 mmHg, or any other significant abnormality on ophthalmic examination (performed by an ophthalmologist); ophthalmological findings secondary to long-standing optic pathway glioma such as optic nerve pallor or strabismus will NOT be considered significant for the purposes of the study
Prior history of non-arterial ischemic optic retinopathy
Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed, progressed, or become refractory to conventional therapy; patients with neurofibromatosis (NF-1) are eligible
Brain metastasis that is located =< 5 mm of the optic chiasm or within the brainstem
Evidence of an optic glioma requiring treatment
Participants with leptomeningeal disease; metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeters (mm) of the optic apparatus (optic nerves and chiasm)
Clinical or neuroimaging evidence of extraocular disease or orbital optic nerve involvement
Patients with a known history of NF1 (Neurofibromatosis Type 1) and either \r\n* A history of a tumor of the central nervous system (astrocytoma or optic glioma), or \r\n* A malignant peripheral nerve sheath tumor with a complete remission of < 1 year are not eligible
Subjects with NF-1 associated optic pathway tumors are excluded if they are actively receiving therapy for the optic pathway tumor or do not meet criteria for PN or malignant solid tumor.
Subjects with NF-1 actively receiving therapy for the optic pathway tumor.
Ophthalmologic conditions:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma may be eligible after discussion with the study chair\r\n* Subjects with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility\r\n* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm)
History of MPNST (malignant peripheral nerve sheath tumor) or any malignancy other than asymptomatic and stable optic nerve glioma
Optic nerve glioma that has resulted in precocious puberty or visual impairment of any degree
Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening (within 28 days before C1D1) and prior radiographic assessments. Participants with radiographically stable, asymptomatic previously irradiated lesions are eligible provided participant is >= 4 weeks beyond completion of cranial irradiation and >= 3 weeks off of corticosteroid therapy. Participants with metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm) are completely excluded
Patients who have previously experienced non-arteritic ischemic optic neuropathy (NAION)
NF1-associated optic pathway glioma (OPG) will be defined as radiographic evidence of glioma along the optic nerve, chiasm, tract or radiation in a child with NF1
Known prior or current retinal or optic nerve disease (eg, Retinitis Pigmentosa, diabetic retinopathy, optic neuritis) based on screening ophthalmology assessment for eligibility.
The tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)
Radiographic evidence of leptomeningeal dissemination, gliomatosis cerebri, infratentorial tumor, or disease at sites remote from the supratentorial brain.
Histologically confirmed diagnosis of supratentorial glioblastoma.
The tumor must be confined to the supratentorial compartment
Tumor must be supratentorial only
The tumor must be supratentorial
Supratentorial mass effect with greater than 5 mm of midline shift or hydrocephalus
Patients with treated supratentorial metastases are allowed if stable, the patient is off steroids and no evidence of intracranial hemorrhage
Patients must have a recurrent supratentorial WHO grade III or IV malignant glioma based on imaging studies
Prior histopathology consistent with a supratentorial WHO grade III or IV malignant glioma
Patients must have a histologically confirmed diagnosis of supratentorial high-grade glioma or supratentorial ependymoma that is recurrent, progressive or refractory
Subjects must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two planes\r\n* This disease must be located primarily in the supratentorial region\r\n* Patients with significant disease that is metastatic outside of the supratentorial region are ineligible
Tumors must be supratentorial in location.
The tumor must be primarily supratentorial in location as determined by diagnostic imaging performed preoperatively
Evidence or suspicion of disease metastatic to sites remote from the supratentorial brain
Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible for study entry
Imaging studies show evidence of recurrent, supratentorial tumor(s); the presence of infratentorial tumor is allowed as long as the patient also has supratentorial disease that is amenable to resection or biopsy
Tumor must have a supratentorial component
The tumor must be supratentorial in location
Evidence or suspicion of disease metastatic to sites remote from supratentorial brain
for intratumoral cohorts, supratentorial HGG (WHO grade III or IV)
Elective craniotomy for supratentorial brain tumors
Undergoing elective craniotomy for supratentorial tumors
Location: supratentorial