Brain metastases requiring steroids Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy). Patients with known symptomatic brain metastases requiring steroids in part 1 or 2 Patients with untreated symptomatic brain metastases may be eligible if symptoms do not require urgent surgery or radiation, and no steroids are necessary Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms (participants with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy) Patients with known symptomatic brain metastases requiring steroids Brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms. Known symptomatic brain metastases requiring steroids. Patients with known symptomatic brain metastases requiring steroids. Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids. Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids. Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids. Participants with symptomatic brain metastases that require chronic steroids are excluded; patients with a history of brain metastases are permitted to enroll as long as they have been treated, off of steroids and have been stable for one month on imaging Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms. Brain metastases requiring steroids Patients with known brain metastases requiring steroids. Participants with symptomatic or progressive brain metastases, or requiring steroids to control symptoms of brain metastases Known untreated, symptomatic, or progressive brain metastases; presence of carcinomatous meningitis; history of intracranial hemorrhage; or brain metastases requiring chronic steroids Any known symptomatic brain metastases requiring steroids. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated. Unstable or symptomatic brain metastases (however, patients with stable or treated brain metastases who do not require steroids at doses above those permitted for control of symptoms may be enrolled) Patients with known symptomatic brain metastases requiring steroids. Brain metastases requiring steroids Brain metastases requiring steroids. Any known symptomatic brain metastases requiring steroids. Patients with known symptomatic brain metastases requiring steroids Brain metastases requiring steroids Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy). Brain metastases that are:\r\n* Progressive or\r\n* Have required any type of therapy (including radiation, surgery or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment Brain metastases with symptoms or requiring treatment Any known symptomatic brain metastases requiring steroids. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy). Participants must not have symptomatic brain metastases or brain metastases requiring steroids; asymptomatic brain metastases not requiring steroids are acceptable Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 1 month (30 days) of enrollment. No symptomatic brain metastasis; (note: patients with treated brain metastasis must be off steroids or on tapering or stable doses of steroids and have completed radiation at least 14 days prior to registration for protocol therapy) Symptomatic brain metastasis requiring corticosteroids Subjects 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 1 week or on physiologic doses of steroids may be enrolled Symptomatic brain metastasis Patients with symptomatic brain involvement Melanoma patients with large or symptomatic brain metastasis, and in whom neurosurgical removal is indicated will not be eligible for this trial Symptomatic or untreated brain metastasis Subjects 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 enrolled Symptomatic brain metastasis The subject has untreated, symptomatic or uncontrolled brain metastasis requiring current treatment including steroids and anti-convulsants; neurosurgical resection of brain metastasis or brain biopsy is permitted if completed at least 3 months before the first dose of study treatment Uncontrolled or symptomatic brain metastasis Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment Patients with uncontrolled symptomatic brain metastases; a scan to confirm absence of brain metastasis is not required Subject has a history of, or current symptomatic brain metastasis. The patient has a primary brain tumor(s) or brain metastasis (unless metastasis is treated and stable for > 28 days). In patients who are symptomatic, a brain scan is required to exclude metastasis. Symptomatic brain metastasis Symptomatic or uncontrolled brain metastasis or epidural disease requiring current treatment including steroids and anti-convulsant Symptomatic brain metastasis Patients with symptomatic brain metastasis requiring escalating doses of steroids Symptomatic uncontrolled brain metastasis Patients who are symptomatic from brain metastasis Symptomatic brain metastasis. Participants with brain metastases: Patients with symptomatic brain metastasis requiring escalating doses of steroids Known active, or symptomatic, brain metastasis Symptomatic brain metastasis; patients with treated brain metastasis must be completely weaned off of steroid therapy for at least 14 days prior to starting protocol therapy No clinical neurologic signs or symptoms of brain metastasis (brain imaging only required for symptomatic individuals per 2014 National Comprehensive Cancer Network [NCCN] Guidelines) Patients with any known brain or leptomeningeal metastases are excluded, even if treated. Untreated or symptomatic brain metastases and leptomeningeal disease Patients with brain metastases (treated or untreated) leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease Patients with evidence of active brain metastases, or active leptomeningeal disease are ineligible; patients with a history of brain metastases must have completed treatment (i.e. surgery or radiation) prior to enrollment Patients with uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases; asymptomatic or treated brain metastases are acceptable Uncontrolled brain or leptomeningeal metastases from plexiform neurofibromas, malignant peripheral nerve sheath tumors, or other cancers (other than proven or probable low grade astrocytomas), including patients who continue to require glucocorticoids for control of symptoms related to brain or leptomeningeal metastases Subjects with known symptomatic brain metastases or leptomeningeal metastases Any known brain or leptomeningeal metastases are excluded, even if treated. Have symptomatic brain metastases or leptomeningeal disease Known brain metastases or leptomeningeal disease involvement. Glioblastoma lesions (primary or locally advanced) are eligible. Known brain or leptomeningeal metastases Subject has known symptomatic brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Subjects with stable asymptomatic brain metastases or leptomeningeal disease are eligible provided that they have not required new treatments for this disease in a 28 day period before the first dose of study drug, and anticonvulsants and steroids have not been administered for a period of 2 weeks prior to the first dose of study drug. Known symptomatic uncontrolled brain or leptomeningeal metastases (Day 1) Patients who have known leptomeningeal metastases or untreated or symptomatic brain metastases; treated, asymptomatic brain metastasis can be included Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Patients who have a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke within the past year Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Current or previously treated brain or leptomeningeal metastases Current or previously treated brain or leptomeningeal metastases Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months Known active brain or leptomeningeal metastases (defined as symptomatic metastases) or continued requirement for glucocorticoids for brain or leptomeningeal metastases; treated, asymptomatic metastases are permitted provided the patient has been off steroids for at least 4 weeks prior to day 1 of study drug Known or suspected leptomeningeal disease; patients with metastases to the brain stem, midbrain, pons or medulla Untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy Patients who have a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, history of stroke within the past year Documented and/or symptomatic or known brain or leptomeningeal metastases Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Uncontrolled brain or leptomeningeal metastases, including those who continue to require glucocorticoids for brain or leptomeningeal metastases Clinical signs of brain involvement or leptomeningeal disease Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Extensive active brain disease including symptomatic brain metastases or presence of leptomeningeal disease Patients with symptomatic brain metastases who have not completed radiation therapy and/or are receiving systemic steroid therapy; patients with leptomeningeal disease will be excluded Brain metastases or active leptomeningeal disease (with the exception of participants with treated epidural disease and no other epidural progression) The participant has documented brain metastases or leptomeningeal disease. Confirmed brain and/or leptomeningeal metastases Patients with known active brain or central nervous system metastases, including leptomeningeal disease; patients with treated and asymptomatic brain metastases may be eligible after discussion with PI Patients must not have symptomatic uncontrolled brain or leptomeningeal metastases. Any brain metastases including leptomeningeal metastases, are excluded, even if treated and stable. Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease Active brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases; treated, asymptomatic metastases are permitted provided the patient has been off steroids for at least 1 month prior to day 1 of study drug Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline) Subject has known or suspected primary brain or leptomeningeal metastases Subject has known symptomatic brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Subjects with stable asymptomatic brain metastases or leptomeningeal disease are eligible if they have not required new treatments for this disease in a 28 day period before the first dose of study drug, and anticonvulsants and steroids have not been administered for a period of 2 weeks prior to the first dose of study drug. Brain metastases or leptomeningeal disease Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Expansion A:\r\n* Brain metastases or leptomeningeal not previously treated with radiation or surgery Metastatic brain or leptomeningeal tumors (treated metastatic brain or leptomeningeal tumors are allowed) Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases A history of or evidence of brain metastases or leptomeningeal disease. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Patients with brain or central nervous system metastases, including leptomeningeal disease Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the following criteria are met: Known symptomatic brain mets or leptomeningeal involvement Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months) Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment No known or suspected (associated neurological signs and symptoms) brain metastases (including leptomeningeal involvement) Patients with brain metastases (treated or untreated) leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease Uncontrolled brain metastases or leptomeningeal involvement; patients with brain metastases are permitted if they have received appropriate therapy and demonstrated control of the brain metastases or leptomeningeal disease following therapy; patients with known brain metastases will require magnetic resonance imaging (MRI) brain to demonstrate disease control prior to enrollment (lack of symptom progression for two weeks off therapeutic doses of steroids, excluding chronic steroids used for control of chronic obstructive pulmonary disease [COPD]) Subjects with brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease Patients with untreated or uncontrolled brain metastases or leptomeningeal disease Current or a prior history of brain metastases or leptomeningeal disease. Must not have rapidly progressive, life-threatening metastases. Symptomatic uncontrolled brain or leptomeningeal metastases Symptomatic uncontrolled brain or leptomeningeal metastases. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Known brain metastases not radiographically stable for ?3 months or leptomeningeal disease Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases; treated brain metastases must have been stable for at least 2 months Uncontrolled brain or all leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases The participant has uncontrolled brain or leptomeningeal metastases Untreated or symptomatic brain metastases or leptomeningeal disease Symptomatic, progressive or corticosteroids-requiring documented brain metastases or leptomeningeal disease involvement. No current symptomatic, untreated, or uncontrolled brain metastases present Clinical or radiologic evidence of new, untreated, and/or progressive brain metastases prior to registration after induction systemic therapy. COHORT A: Previously untreated asymptomatic brain metastases Untreated or clinically active melanoma brain metastases. Participant has untreated brain or meningeal metastases. Active or untreated brain metastases Patients with untreated known brain metastases, or treated brain metastases that are clinically unstable History of brain metastases or who currently have treated or untreated brain metastases Untreated brain metastases Untreated brain metastases, if not planned to be treated in this course of radiation therapy Untreated brain metastases Known untreated or symptomatic brain metastases Untreated, progressing, or symptomatic brain metastases Known active and/or untreated brain metastases Symptomatic or untreated brain metastases One to 4 untreated metastatic brain lesions Metastatic melanoma or non-squamous NSCLC with untreated brain metastases Progressive, symptomatic untreated brain metastases Must not have untreated brain metastases Symptomatic and/or untreated Brain Metastases Untreated brain metastases Patients with untreated brain or meningeal metastases Untreated, progressing, or symptomatic brain metastases Untreated brain metastases (or local treatment of brain metastases within the last 6 months) Patients with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including those used to control symptoms, within 1 month of first dose Untreated or symptomatic brain metastases Untreated brain metastases Untreated or symptomatic brain metastases Patients with untreated brain metastases No symptomatic, untreated, or uncontrolled brain metastases present Known untreated brain metastases Active and/or untreated CNS disease or non-stable brain metastases Untreated or progressive brain metastases; patients with treated brain metastases not requiring chronic corticosteroids for symptom control are eligible Untreated or progressive brain metastases Previously untreated brain metastases. Patients with untreated or progressing brain metastases Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible Untreated and/or uncontrolled brain metastases. Untreated brain metastases (or local treatment of brain metastases within the last 6 months) Untreated brain metastases. Patients with active or untreated brain metastases; treated brain metastases must have been stable for at least 2 months Untreated or progressive brain metastases; patients with treated brain metastases not requiring chronic corticosteroids for symptom control are eligible Untreated brain metastases Patients with untreated symptomatic brain metastases will be excluded from this study; those with treated brain metastases or untreated but asymptomatic sub-centimeter brain metastases will be allowed as long as they are neurologically asymptomatic and off steroids Subjects with previously untreated or uncontrolled brain metastases. The participant has an untreated brain tumor Known brain metastases, or untreated meningeal/dural disease Untreated brain metastases. (Brain metastases that have been treated, which no longer require corticosteroid therapy and are without progression by MRI at least 6 weeks after definitive therapy are acceptable.) Has known untreated or symptomatic brain metastases; Untreated brain metastasis; patients with treated brain metastases who are off steroids are eligible Untreated brain metastases Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms Brain metastases that are untreated or symptomatic or require any radiation, surgery,\n or steroid therapy to control symptoms from brain metastases within 1 month of\n randomization Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery or other therapy to control symptoms from brain metastases within 2 months prior to first dose of MEDI4276. Untreated brain metastases; brain metastases =< 1 cm and not associated with any focal neurologic deficits are allowed Untreated brain metastases Active, untreated brain metastases Untreated brain metastases Patients with known untreated brain metastases Active or untreated brain metastases Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms Untreated brain metastases (or local treatment of brain metastases within the last three months) Untreated brain metastases Brain metastases that are symptomatic or untreated or that require current therapy. Participant has untreated brain or meningeal metastases. Symptomatic and/or untreated brain metastases Untreated brain metastases Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms Patients with known untreated and uncontrolled brain metastases are excluded. However, brain-imaging studies are not required for eligibility if the patient has no neurological signs or symptoms.