Spray a 6-quart slow cooker with nonstick cooking spray. Trim the excess fat from the brisket, leaving a ¼-inch to ½-inch layer. Pat the meat dry with a paper towel, then rub salt and black pepper on both sides.
Coat a 12 to 14-inch cast iron skillet with oil and heat over medium-high, then reduce to medium. Add the brisket and cook until browned, about 3 to 5 minutes per side, adjusting the heat as needed. Place the brisket in the slow cooker and do not clean out the skillet.
In a small bowl, combine the brown sugar, chili powder, paprika, garlic powder, and cayenne. Sprinkle the rub over the brisket, turning to coat, then arrange it fat-side up. Pour the BBQ sauce and Worcestershire around the sides of the brisket.
In the same skillet, cook the onion over medium-high heat just until browned, about 1 to 2 minutes per side. Transfer the onion to the slow cooker. Add the beer to the skillet and cook over low heat for 1 to 2 minutes, scraping up the browned bits. Pour the beer and drippings into the slow cooker.
Cover and cook until tender, about 3 to 4 hours on HIGH or 6 to 8 hours on LOW. The meat should reach about 185-190°F when you pull it, since the temperature keeps rising as it rests.
Place the brisket on a cutting board and let it stand for 15 minutes. Slice against the grain, then taste and season with additional salt and pepper if needed. Serve on rolls with extra BBQ sauce, the onions from the pot, coleslaw, and sliced pickles if desired.