Patients with known active brain metastases should be excluded from this clinical trial; patients with prior treated brain metastases are allowed, providing that they were not accompanied by seizures and that a baseline brain magnetic resonance imaging (MRI) scan prior to study entry demonstrates no current evidence of brain metastases; all patients with central nervous system (CNS) metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollmentXx_NEWLINE_xXPatients with brain metastases are ineligible; all patients must have a pretreatment CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registrationXx_NEWLINE_xXDiagnosis of a primary brain tumor treated with at least one of the following:* Neurosurgical resection of the brain tumor* Cranial irradiation* Any chemotherapy to treat the brain tumorXx_NEWLINE_xXPatients with known active brain metastases are excluded; patients with a history of central nervous system (CNS) metastases that have been treated must be stable with no symptoms for > 3 months after completion of that treatment and off steroid treatment, with image documentation required prior to study enrollmentXx_NEWLINE_xXKnown central nervous system (CNS) or brain metastasis that are either symptomatic or untreated; Note: patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis* Note: patients with CNS metastases that have been treated and are stable without symptoms for >= 4 weeks after completion of treatment are eligibleXx_NEWLINE_xXPatients with active or untreated brain metastases; treated brain metastases must have been stable for at least 2 monthsXx_NEWLINE_xXAt least 1 measurable unirradiated parenchymal brain metastasis within 21 days prior to study entry; patients who are to undergo SRS must have no more than 10 brain metastases; there is no limit on number of brain metastases for WBRT; the minimum size as measured on T1-weighted gadolinium-enhanced MRI must be as follows according to the number of brain metastases:* For a single solitary lesion the size must be >= 10 mm* For 2 or more lesions, the size of at least 2 of the lesions must be >= 5 mm* Patients may also have the following provided the size requirements above are met:** Progressive parenchymal brain metastasis following stereotactic radiosurgery for 1-3 brain metastases, with at least 1 new measurable brain lesion** Progressive parenchymal brain metastasis following surgical resection of 1-3 brain metastases, with at least 1 measurable brain lesionXx_NEWLINE_xXPatients with active brain metastases or carcinomatous meningitis or epidural disease are excluded from this clinical trial; subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation who are asymptomatic and have remained stable for 4 weeks and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibilityXx_NEWLINE_xXThe participant has a primary brain tumorXx_NEWLINE_xXThe participant has active brain metastases or epidural disease; participants with brain metastases previously treated with whole brain radiation or radiosurgery or participants with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 4 weeks before starting study treatment are eligible; participants with treated brain metastasis should not take enzyme-inducing anticonvulsive therapies (EIACDs) within 2 weeks of registration, though non-enzyme inducing anticonvulsive drugs such as levetiracetam are allowed; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans for participants with known brain metastases is required to confirm eligibilityXx_NEWLINE_xXAll patients must undergo a CT or MRI of the brain within 42 days prior to registration; patients with asymptomatic brain metastases or previously treated brain metastases that are stable (i.e. not requiring corticosteroids) at the time of registration will be eligibleXx_NEWLINE_xXSubjects with inactive central nervous system (CNS) metastasis are eligible; inactive CNS metastasis is defined as: no signs of cerebral edema after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatmentXx_NEWLINE_xXStudy participants with brain metastases are excluded unless these have been definitively treated and are radiographically stable for at least 1 month; the study participant must also demonstrate a stable physical exam and must have discontinued systemic steroids for treatment of edema related to brain metastases or treatment for over 7 daysXx_NEWLINE_xXPresence of symptomatic brain metastases at time of study consent process; patients with history of treated brain metastases are eligible if they are not symptomatic at the time of study enrollmentXx_NEWLINE_xXSymptomatic or untreated leptomeningeal or brain metastases or spinal cord compressionXx_NEWLINE_xXPatients with known brain metastases should be excluded from this clinical trial; exception: patients with brain metastases will be allowed on study if they have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of central nervous system (CNS) disease progression as determined by computed tomography (CT) or magnetic resonance imaging (MRI) within 21 days prior to the first dose of study drugXx_NEWLINE_xXNo history of intracranial brain metastasisXx_NEWLINE_xXPatients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registrationXx_NEWLINE_xXNo current symptomatic, untreated, or uncontrolled brain metastases presentXx_NEWLINE_xXKnown brain metastasesXx_NEWLINE_xXNo symptomatic, untreated, or uncontrolled brain metastases presentXx_NEWLINE_xXKnown brain metastases (even if treated)Xx_NEWLINE_xXSymptomatic or untreated leptomeningeal or brain metastases or spinal cord compressionXx_NEWLINE_xXStage 1 solid tumor and stage 2 endometrial and ovarian cancer participants with known central nervous system (CNS) metastatic lesions which are symptomatic and/or growing; patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll; brain metastasis must be stable for 1 month with verification by imaging (brain MRI completed at screening demonstrating no current evidence of progressive brain metastases); CNS imaging will not be mandated for asymptomatic patients with no history of CNS metastasesXx_NEWLINE_xXPatients must not have brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 7 days prior to registrationXx_NEWLINE_xXNo radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapyXx_NEWLINE_xXPatients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery [SRS]) could be eligible; patients must not have taken any steroids =< 10 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligibleXx_NEWLINE_xXPatients are ineligible if they have any currently active CNS metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery [SRS]) could be eligible to proceed; patients crossing over from dabrafenib/trametinib to nivolumab (nivo)/ipilimumab (ipi) must not have taken any steroids =< 10 days prior to registration for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases are ineligibleXx_NEWLINE_xXBrain metastasesXx_NEWLINE_xXThe subject has a primary brain tumorXx_NEWLINE_xXKnown brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before the first dose of study treatment; eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatmentXx_NEWLINE_xXPatients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 3 months prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatmentXx_NEWLINE_xXThe subject has active brain metastases or epidural disease; subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced CT or magnetic resonance imaging (MRI) scans for subjects with known brain metastases is required to confirm eligibilityXx_NEWLINE_xXActive brain metastasis or leptomeningeal disease; patients with known brain metastases are allowed if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 12 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administrationXx_NEWLINE_xXPatients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration; patient must not have symptomatic brain metastases or evidence of leptomeningeal carcinomatosis; patients with asymptomatic brain metastases are eligible if off of steroids for at least 7 days prior to registration without development of symptomsXx_NEWLINE_xXHistory or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, any brain metastases and/or epidural disease, or history of cerebrovascular accident (cerebrovascular accident [CVA], stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatmentXx_NEWLINE_xXPatients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan for at least 4 weeks following treatment and within 4 weeks prior to randomization are eligible; patients must not have taken any steroids =< 14 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligibleXx_NEWLINE_xXBrain metastases outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior to Step 1 registration; an allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain metastases; however, the brain metastases could not have been within 5 mm of either hippocampusXx_NEWLINE_xXPatients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 4 weeks prior to start of treatmentXx_NEWLINE_xXParticipants with known brain metastases or leptomeningeal metastases must be excluded unless they qualify for enrollment as described below because of poor prognosis and concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; participants with brain metastases are permitted if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks or more after treatment is complete and within 4 weeks prior to the first dose of nivolumab administrationXx_NEWLINE_xXThe participant has a primary brain tumorXx_NEWLINE_xXPatients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study; screening imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study drugXx_NEWLINE_xXPatients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events; patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study drugXx_NEWLINE_xXPatients with active or untreated brain metastases or leptomeningeal metastases are excluded from this clinical trial; NOTE: patients with previously treated brain metastases must have stable neurologic status and magnetic resonance imaging (MRI) imaging following local therapy (surgery or radiation) for at least 4 weeks, with no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration (stable low dose dexamethasone allowed at discretion of protocol chair)Xx_NEWLINE_xXPatient does not have known brain metastases (testing optional)Xx_NEWLINE_xXPatients with known brain metastases should be excluded from this clinical trial; however, patients with previously treated and stable brain metastases are eligible as long as they are no longer requiring steroids, completed radiation therapy more than 2 weeks prior to the first dose of study regimen and have no seizures or worsening neurologic symptomsXx_NEWLINE_xXPatients with untreated brain metastases are allowed provided that the patient is clinically asymptomatic and stable; patients with a prior history of symptomatic brain metastases are eligible provided:* The brain metastases have been treated* The patient is asymptomatic from the brain metastases at enrollment* Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration* The brain metastases are stable on pre-registration imagingXx_NEWLINE_xXPatients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical trial; screening brain MRI (or CT if MRI contraindicated) will be required for patients with recurrent NSCLC, TNBC, or SCLC; brain MRI (or CT if MRI contraindicated) is required for PDAC if clinically suspected by patient�s symptoms or neurological exam; should patient found to have brain metastasis, treatment of brain metastasis must precede the participation in this study; for patients with known and treated brain metastases is allowed in this study if they fulfill the following criteria:* The lesions have improved or remained stable radiographically and clinically for at least 6 weeks after completion of brain irradiation or stereotactic brain radiosurgery and off steroids for at least 6 weeksXx_NEWLINE_xXPatients with a prior history of brain metastases are eligible provided:* The brain metastases have been treated * The patient is asymptomatic from the brain metastases* Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration * The brain metastases are stable on pre-registration imagingXx_NEWLINE_xXHave distant metastasesXx_NEWLINE_xXPatients with a prior history of brain metastases are eligible provided:* The brain metastases have been treated* The patient is asymptomatic from the brain metastases* Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration* The brain metastases are stable on pre-registration imagingXx_NEWLINE_xXPatients who present with symptomatic brain radionecrosis after they have received radiosurgery for brain metastases from primary solid tumor including but not limited to lung, breast, colorectal cancer but excluding melanoma, choriocarcinoma, renal cell carcinoma or gliomasXx_NEWLINE_xXPatients with a prior history of brain metastases are eligible provided:* The brain metastases have been treated* The patient is asymptomatic from the brain metastases* Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registrationXx_NEWLINE_xXPatients with a history of treated brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)Xx_NEWLINE_xXPatients with brain metastases are allowed provided that:* No leptomeningeal disease is present* Intracranial disease is controlled by prior local therapies (craniotomy, stereotactic radiosurgery, whole brain irradiation), as evidenced by brain MRI 4 weeks post treatment indicating no new intracranial disease* Stable or decreasing dose of steroids provided patient on =< 20 mg of prednisone or its equivalent dailyXx_NEWLINE_xXExtensive active brain disease including symptomatic brain metastases or the presence of leptomeningeal disease, and all patients with infratentorial tumors* Note: patients with brain metastasis after definitive therapy with surgery or stereotactic radiation and stable off steroids for > 4 weeks are eligible as are patients with asymptomatic brain metastasis as long as less than 1 cm and thus deemed as not requiring therapy by the primary physician and the lesions(s) are not infratentorialXx_NEWLINE_xXPatients with known brain metastases must either meet the additional criteria and enroll as part of the Progressive Brain Metastases Cohort, or have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 14 days of stable neurologic function prior to registration; patients with previously incidentally discovered or asymptomatic brain metastasis(es) must receive surgical excision and/or radiation therapy prior to registration; patients with progressive brain metastases following prior treatment are not eligible for the Standard Cohort, but may be considered for the Progressive Brain Metastases CohortXx_NEWLINE_xXProgressive Brain Metastases Cohort* S1416 is one study with two cohorts; patients who have progressive brain metastases after surgical excision and/or intracranial radiation will be in the Progressive Brain Metastases Cohort and will require a baseline magnetic resonance imaging (MRI); patients with previously treated brain metastases, stable disease and stable neurologic function for 14 days prior to trial registration will be in the Standard Cohort and may obtain MRI of the brain at the physician�s discretion; randomization and treatment is the same for both cohorts* In addition to all of the previous eligibility criteria, patients with progressive brain metastases who do not satisfy the conditions to enroll in the standard cohort (neurologic stability for 14 days following surgery and/or radiation therapy) must also meet the following criteria to enroll as part of the brain metastases cohort:** Patients with progressive brain metastases must have a baseline brain MRI within 28 days prior to registration; brain metastases must be progressive and >= 10 mm in longest dimension on radiographic imaging AFTER prior intracranial radiation (IR) therapy (i.e., whol brain radiation therapy [WBRT], stereotactic radiosurgery [SRS], gamma knife [GK] or local equivalent); patients must not have evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology; discrete dural metastases are permitted; there must be no evidence of hemorrhage or impending herniation on baseline brain imaging; patients with contraindication to gadolinium-enhanced MRI imaging are not eligible** Patients must be on a stable or decreasing dose of steroids for >= 7 days prior to registration** If patient had an open brain biopsy, at least 28 days must have elapsed between biopsy and registration** Patients enrolling in the Progressive Brain Metastases Cohort can have received up to 3 prior lines of cytotoxic chemotherapy for metastatic disease; note that for enrollment in the standard cohort, patients must have had =< 1 prior cytotoxic regimen for metastatic diseaseXx_NEWLINE_xXPatients with unstable brain metastases should be excluded; however, patients with known brain metastases may participate in this clinical trial if they are clinically stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are on a stable or decreasing dose of steroids for at least 14 days prior to trial treatmentXx_NEWLINE_xXSubjects with symptomatic brain metastases will be excluded from trial secondary to poor prognosis; however, subjects who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for at least 3 months may be enrolledXx_NEWLINE_xXPatients must not have history of brain metastasesXx_NEWLINE_xXDISEASE RELATED CRITERIA: Patients must not have known brain metastases, leptomeningeal carcinomatosis or spinal cord compression unless: (1) metastases have been locally treated (including stereotactic body radiation therapy [SBRT], whole brain radiotherapy [WBRT], and surgical resection) and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to registrationXx_NEWLINE_xXPatients must not have known brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 14 days prior to registrationXx_NEWLINE_xXPrior radiotherapy for patients with brain metastases prior to enrollment is acceptable.Xx_NEWLINE_xXPatients with brain metastases are eligible if these lesions have been previously treated and the patients have no clinical or radiographic evidence of progression within 30 days prior to enrollment.Xx_NEWLINE_xXClinical or radiologic evidence of new, untreated, and/or progressive brain metastases prior to registration after induction systemic therapy.Xx_NEWLINE_xXPatients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 28 days prior to registration and have stable disease at time of registration; metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration; patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registrationXx_NEWLINE_xXPatients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse eventsXx_NEWLINE_xXPatients with untreated brain metastases, spinal cord compression, or leptomeningeal carcinomatosis should be excluded from this clinical trial; patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases; these imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression); in addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of =< 10 mg/day of prednisone or its equivalent (and anti-convulsants) for at least 14 days prior to the start of treatmentXx_NEWLINE_xXPatients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans are excluded from this clinical trial; while screening brain MRI is not required, it should be performed if clinically indicated at the discretion of the treating investigator; should patient found to have brain metastasis, treatment of brain metastasis must precede the participation in this studyXx_NEWLINE_xXFor patients with known and treated brain metastases is allowed in this study if they fulfill ALL of the following criteria:* The lesions have remained radiologically stable for at least six weeks after completion of brain irradiation or stereotactic brain radiosurgery, and must remain stable at the time of study entry* There is no mass effect present radiologically and no steroids requirement for symptom control for more than 4 weeksXx_NEWLINE_xXPatients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:* Brain metastases which have been treated* No evidence of disease progression for >= 3 months before the first dose of study drug* No hemorrhage after treatment* Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228* No ongoing requirement for dexamethasone or anti-epileptic drugsXx_NEWLINE_xXPatients may have brain metastases if all lesions have been treated with stereotactic radiation therapy, craniotomy, or gamma knife therapy with no evidence of progression (demonstrated by identical imaging modality for 2 consecutive assessments/scans [magnetic resonance imaging (MRI) or CT scans], at least 4 weeks apart) and have not required steroids for at least 14 days prior to registrationXx_NEWLINE_xXPatients must have at least one measurable CNS lesion that is asymptomatic, untreated, and does not require local therapy at the time of enrollment; measurable CNS disease is defined as a brain metastasis that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 5 mm (>= 0.5 cm) with brain magnetic resonance imaging (MRI); if the lesion is 5-10 mm in size and is the only measurable disease, MRI imaging must be performed with 1.5 mm slice thickness or less; a history of previously treated brain metastases is allowed, however any lesion present at the time of whole brain radiotherapy or included in the stereotactic radiotherapy field (or within 2 mm of the treated lesion) will NOT be considered �untreated� unless it is new or documented to have progressed unequivocally since treatmentXx_NEWLINE_xXSymptomatic brain metastasesXx_NEWLINE_xXPatients with brain metastases for whom complete surgical resection is clinically appropriateXx_NEWLINE_xXPatients with known active central nervous system (CNS) metastases are ineligible; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastasesXx_NEWLINE_xXPatients must be able to undergo magnetic resonance imaging (MRI) of the brain with gadoliniumXx_NEWLINE_xXPatients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)Xx_NEWLINE_xXSymptomatic or untreated leptomeningeal or brain metastases or spinal cord compressionXx_NEWLINE_xXPatients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the 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 enrollment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 daysXx_NEWLINE_xX