Spray a 6-quart slow cooker with nonstick cooking spray. Trim the excess fat from the brisket, leaving a ¼-inch to ½-inch-thick layer. Pat the meat dry with a paper towel; rub salt and black pepper on both sides.
Coat a 12-14-inch cast iron skillet with oil, and heat over medium-high heat. Reduce the heat to medium. Add the brisket; cook until browned, about 3-5 minutes per side (adjust the heat as needed). Place the brisket in the slow cooker (do not clean out the skillet).
In a small bowl, combine the brown sugar, chili powder, paprika, garlic powder, and cayenne. Sprinkle the seasoning rub on the brisket, turning to coat. Arrange the brisket fat-side up. Pour the bbq sauce and Worcestershire sauce around the sides of the brisket.
In the same cast iron skillet, cook the onion over medium-high heat, just until browned, about 1-2 minutes per side. Transfer the onion to the slow cooker. Add the beer to the skillet and cook over low heat for about 1-2 minutes, scraping the browned bits from the bottom of the pan. Pour the beer and other drippings from the skillet into the slow cooker.
Cover the slow cooker and cook the brisket until tender, about 3-4 hours on HIGH or 6-8 hours on LOW. The meat should reach an internal temperature of about 195-200°F (just remember that the temperature will continue to rise as it rests, so you can pull it out of the slow cooker once it reaches about 185-190°F).
Place the brisket on a cutting board; let it stand for 15 minutes. Slice the brisket against the grain. Taste and season with additional salt and pepper, if necessary. Serve on sandwich rolls with extra bbq sauce, the onions from the pot, coleslaw, and/or sliced pickles if desired.